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Potent Neuroprotective Effect of Selenium on Cerebral Ischemic Stroke

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Tara Walker,Perry Bartlett
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Ischemic stroke remains a leading cause of death and disability worldwide despite recent progress in recanalization using modern thrombectomy to remove the thrombus or conventional tissue-plasminogen activator (t-PA) to dissolve it. Moreover, functional outcomes after successful reperfusion therapy are still suboptimal in many patients. Reperfusion-induced oxidative stress, post-stroke inflammation, dysbiosis, and secondary neurodegeneration are believed to impede functional recovery after stroke. Therefore, discovering novel therapies that can be used in conjunction with reperfusion treatment to mitigate post-stroke deficits and facilitate post-stroke recovery is highly desirable. In this study, I evaluate the potential neuroprotective effect of selenium following ischemic stroke, specifically, delivery after the reperfusion to rigorously mimic the clinical situation.


Selenium is an indispensable trace element for mammals. By incorporating into selenoproteins, it forms a critical defence against cellular oxidative stress. In light of its antioxidant ability, the potential neuroprotective effects of selenium on ischemic stroke have been proposed for decades but have yet to be fully determined. While several clinical studies have identified the negative correlation between circulating selenium levels and the incidence of ischemic stroke, the correlation between circulating selenium levels and stroke prognosis remains elusive. And whether selenium supplementation after stroke is beneficial remains unknown.


Here, I found that selenomethionine (Se-Met), the most abundant form of selenium in food, confers a potent neuroprotective effect in two mouse models of cerebral ischemic stroke. Firstly, using an endothelin-1 (ET-1)-induced hippocampal stroke model, I found that dietary selenium supplementation ameliorated post-stroke spatial learning and memory deficits observed in the active place avoidance task. These results were corroborated in separate cohorts of mice using additional spatial memory tasks involving novel object recognition, novel object location, forced alternation Y-maze, and contextual fear conditioning. Interestingly, and increasing its clinical relevance, selenium treatment immediately after stroke had similar efficacy as 4 weeks of pre-treatment. Additionally, using a transgenic knock-in DCXDTR mouse strain, I demonstrated that the effect of selenium in this stroke model is adult neurogenesis-dependent, as the ablation of newborn neurons abrogated the selenium-mediated cognitive improvement.


Next, to further evaluate the neuroprotective effect of selenium, I used a canonical middle cerebral artery occlusion (MCAO) model of focal ischemic stroke and demonstrated that delayed-selenium treatment (2 hours after the reperfusion) significantly reduced the cerebral infarct volume and enhanced post-stroke motor function in the acute phase after stroke. As a result of its antioxidant capacity, selenium treatment reinstated cellular redox balance, prevented lipid peroxidation, and therefore protected neurons against ischemia/reperfusion insult. Moreover, long-term dietary selenium supplementation after stroke remarkably rescued spatial learning and memory deficits, alleviated systematic inflammation, stimulated the secretion of intrinsic neuroprotective protein fibroblast growth factor-21 (FGF-21), prevented secondary neurodegeneration and post-stroke dysbiosis, and diminished gut microbe-derived circulating trimethylamine N-oxide (TMAO).


Collectively, this study confirmed the potent neuroprotective effects of selenium using two mouse models of cerebral ischemia and revealed multiple mechanisms of selenium action, highlighting its promising translational prospect. Further pre-clinical and clinical investigation is therefore warranted to definitively establish the optimum dose and efficacy.

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[Abeysinghe, H.C.S., and Roulston, C.L. (2018). A Complete Guide to Using the Endothelin-1 Model of Stroke in Conscious Rats for Acute and Long-Term Recovery Studies. In Traumatic and Ischemic Injury: Methods and Protocols, B. Tharakan, ed. (New York, NY: Springer New York), pp. 115-133.Adusumilli, V.S., Walker, T.L., Overall, R.W., Klatt, G.M., Zeidan, S.A., Zocher, S., Kirova, D.G., Ntitsias, K., Fischer, T.J., Sykes, A.M., et al. (2021). ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence. Cell Stem Cell 28, 300-314 e306.Adusumilli, V.S., Walker, T.L., Overall, R.W., Klatt, G.M., Zocher, S., Zeidan, S.A., Fischer, T.J., Sykes, A.M., Reinhardt, S., and Dahl, A. (2019). Redox potential defines functional states of adult hippocampal stem cells. bioRxiv, 606186.Ahmad, A., Khan, M.M., Ishrat, T., Khan, M.B., Khuwaja, G., Raza, S.S., Shrivastava, P., and Islam, F. (2011). Synergistic effect of selenium and melatonin on neuroprotection in cerebral ischemia in rats. Biol Trace Elem Res 139, 81-96.Ahmad, S., Elsherbiny, N.M., Haque, R., Khan, M.B., Ishrat, T., Shah, Z.A., Khan, M.M., Ali, M., Jamal, A., Katare, D.P., et al. (2014). Sesamin attenuates neurotoxicity in mouse model of ischemic brain stroke. Neurotoxicology 45, 100-110.Akbaraly, T.N., Hininger-Favier, I., Carriere, I., Arnaud, J., Gourlet, V., Roussel, A.M., and Berr, C. (2007). Plasma selenium over time and cognitive decline in the elderly. Epidemiology 18, 52-58.Akers, K.G., Martinez-Canabal, A., Restivo, L., Yiu, A.P., De Cristofaro, A., Hsiang, H.L., Wheeler, A.L., Guskjolen, A., Niibori, Y., Shoji, H., et al. (2014). Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science 344, 598-602.Albers, G.W., Marks, M.P., Kemp, S., Christensen, S., Tsai, J.P., Ortega-Gutierrez, S., McTaggart, R.A., Torbey, M.T., Kim-Tenser, M., Leslie-Mazwi, T., et al. (2018). Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med 378, 708-718.Alehagen, U., Johansson, P., Aaseth, J., Alexander, J., and Brismar, K. (2017). Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. PLoS One 12, e0178614.Alim, I., Caulfield, J.T., Chen, Y., Swarup, V., Geschwind, D.H., Ivanova, E., Seravalli, J., Ai, Y., Sansing, L.H., Ste Marie, E.J., et al. (2019). Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke. Cell 177, 1262-1279 e1225.Almeida, J.R., Souza, G.R., Silva, J.C., Saraiva, S.R., Junior, R.G., Quintans Jde, S., Barreto Rde, S., Bonjardim, L.R., Cavalcanti, S.C., and Quintans, L.J., Jr. (2013). Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice. ScientificWorldJournal 2013, 808460.Altman, J., and Das, G.D. (1965). Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124, 319-335.Ambrosone, C.B., Zirpoli, G.R., Hutson, A.D., McCann, W.E., McCann, S.E., Barlow, W.E., Kelly, K.M., Cannioto, R., Sucheston-Campbell, L.E., Hershman, D.L., et al. (2019). Dietary Supplement Use During Chemotherapy and Survival Outcomes of Patients With Breast Cancer Enrolled in a Cooperative Group Clinical Trial (SWOG S0221). J Clin Oncol, JCO1901203.Anacker, C., and Hen, R. (2017). Adult hippocampal neurogenesis and cognitive flexibility - linking memory and mood. Nat Rev Neurosci 18, 335-346.Anacker, C., Luna, V.M., Stevens, G.S., Millette, A., Shores, R., Jimenez, J.C., Chen, B., and Hen, R. (2018). Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus. Nature 559, 98-102.Arvidsson, A., Collin, T., Kirik, D., Kokaia, Z., and Lindvall, O. (2002). Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8, 963-970.Ben Abdallah, N.M., Slomianka, L., and Lipp, H.P. (2007). Reversible effect of X-irradiation on proliferation, neurogenesis, and cell death in the dentate gyrus of adult mice. Hippocampus 17, 1230-1240.Benjamin, E.J., Blaha, M.J., Chiuve, S.E., Cushman, M., Das, S.R., Deo, R., de Ferranti, S.D., Floyd, J., Fornage, M., Gillespie, C., et al. (2017). Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation 135, e146-e603.Berg, D.A., Su, Y., Jimenez-Cyrus, D., Patel, A., Huang, N., Morizet, D., Lee, S., Shah, R., Ringeling, F.R., Jain, R., et al. (2019). A Common Embryonic Origin of Stem Cells Drives Developmental and Adult Neurogenesis. Cell 177, 654-668 e615.Bersuker, K., Hendricks, J.M., Li, Z.P., Magtanong, L., Ford, B., Tang, P.H., Roberts, M.A., Tong, B.Q., Maimone, T.J., Zoncu, R., et al. (2019). The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature 575, 688-+.Berzelius, J. (1818). Undersökning af en ny Mineral-kropp, funnen i de orenare sorterna af det i Falun tillverkade svaflet. Afhandlingar i fysik, kemi och mineralogi 6, 42-144.Biernaskie, J., Corbett, D., Peeling, J., Wells, J., and Lei, H. (2001). A serial MR study of cerebral blood flow changes and lesion development following endothelin-1-induced ischemia in rats. Magn Reson Med 46, 827-830.Bleys, J., Navas-Acien, A., and Guallar, E. (2008a). Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults. Arch Intern Med 168, 404-410.Bleys, J., Navas-Acien, A., and Guallar, E. (2008b). Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults. Archives of Internal Medicine 168, 404-410.Boldrini, M., Fulmore, C.A., Tartt, A.N., Simeon, L.R., Pavlova, I., Poposka, V., Rosoklija, G.B., Stankov, A., Arango, V., Dwork, A.J., et al. (2018). Human Hippocampal Neurogenesis Persists throughout Aging. Cell Stem Cell 22, 589-599 e585.Bonaguidi, M.A., Wheeler, M.A., Shapiro, J.S., Stadel, R.P., Sun, G.J., Ming, G.L., and Song, H. (2011). In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell 145, 1142-1155.Bordiuk, O.L., Smith, K., Morin, P.J., and Semenov, M.V. (2014). Cell proliferation and neurogenesis in adult mouse brain. PLoS One 9, e111453.Brines, M.L., Ghezzi, P., Keenan, S., Agnello, D., de Lanerolle, N.C., Cerami, C., Itri, L.M., and Cerami, A. (2000). Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A 97, 10526-10531.Bruning, C.A., Prigol, M., Luchese, C., Jesse, C.R., Duarte, M.M.M.F., Roman, S.S., and Nogueira, C.W. (2012). Protective Effect of Diphenyl Diselenide on Ischemia and Reperfusion-Induced Cerebral Injury: Involvement of Oxidative Stress and Pro-Inflammatory Cytokines. Neurochem Res 37, 2249-2258.Burk, R.F., and Hill, K.E. (2009). Selenoprotein P-expression, functions, and roles in mammals. Biochim Biophys Acta 1790, 1441-1447.Burk, R.F., and Hill, K.E. (2015). Regulation of Selenium Metabolism and Transport. Annu Rev Nutr 35, 109-134.Burk, R.F., Hill, K.E., Motley, A.K., Winfrey, V.P., Kurokawa, S., Mitchell, S.L., and Zhang, W.Q. (2014). Selenoprotein P and apolipoprotein E receptor-2 interact at the blood-brain barrier and also within the brain to maintain an essential selenium pool that protects against neurodegeneration. Faseb J 28, 3579-3588.Cao, J.Y., and Dixon, S.J. (2016). Mechanisms of ferroptosis. Cell Mol Life Sci 73, 2195-2209.Capra, S. (2006). Nutrient reference values for Australia and New Zealand: Including recommended dietary intakes.Cardoso, B.R., Hare, D.J., Bush, A.I., and Roberts, B.R. (2017). Glutathione peroxidase 4: a new player in neurodegeneration? Mol Psychiatry 22, 328-335.Ceanga, M., Dahab, M., Witte, O.W., and Keiner, S. (2021). Adult Neurogenesis and Stroke: A Tale of Two Neurogenic Niches. Front Neurosci 15, 700297.Ceanga, M., Keiner, S., Grunewald, B., Haselmann, H., Frahm, C., Couillard-Despres, S., Witte, O.W., Redecker, C., Geis, C., and Kunze, A. (2019). Stroke Accelerates and Uncouples Intrinsic and Synaptic Excitability Maturation of Mouse Hippocampal DCX(+) Adult-Born Granule Cells. J Neurosci 39, 1755-1766.Chasteen, N.D., and Williams, J. (1981). The Influence of Ph on the Equilibrium Distribution of Iron between the Metal-Binding Sites of Human Transferrin. Biochemical Journal 193, 717-727.Chen, B., Chen, Z., Liu, M., Gao, X., Cheng, Y., Wei, Y., Wu, Z., Cui, D., and Shang, H. (2019). Inhibition of neuronal ferroptosis in the acute phase of intracerebral hemorrhage shows long-term cerebroprotective effects. Brain Res Bull 153, 122-132.Chen, Y.J., Wallace, B.K., Yuen, N., Jenkins, D.P., Wulff, H., and O'Donnell, M.E. (2015). Blood-Brain Barrier KCa3.1 Channels Evidence for a Role in Brain Na Uptake and Edema in Ischemic Stroke. Stroke 46, 237-244.Chen, Y.Y., Ye, Z.S., Xia, N.G., and Xu, Y. (2022). TMAO as a Novel Predictor of Major Adverse Vascular Events and Recurrence in Patients with Large Artery Atherosclerotic Ischemic Stroke. Clin Appl Thromb Hemost 28, 10760296221090503.Chidambaram, S.B., Rathipriya, A.G., Mahalakshmi, A.M., Sharma, S., Hediyal, T.A., Ray, B., Sunanda, T., Rungratanawanich, W., Kashyap, R.S., Qoronfleh, M.W., et al. (2022). The Influence of Gut Dysbiosis in the Pathogenesis and Management of Ischemic Stroke. Cells 11.Christie, K.J., and Turnley, A.M. (2012). Regulation of endogenous neural stem/progenitor cells for neural repair-factors that promote neurogenesis and gliogenesis in the normal and damaged brain. Front Cell Neurosci 6, 70.Codd, L.N., Blackmore, D.G., Vukovic, J., and Bartlett, P.F. (2020). Exercise reverses learning deficits induced by hippocampal injury by promoting neurogenesis. Sci Rep 10, 19269.Collaborators, G.B.D.S. (2021). Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 20, 795-820.Conour, J.E., Graham, W.V., and Gaskins, H.R. (2004). A combined in vitro/bioinformatic investigation of redox regulatory mechanisms governing cell cycle progression. Physiol Genomics 18, 196-205.Conrad, M., and Proneth, B. (2020). Selenium: Tracing Another Essential Element of Ferroptotic Cell Death. Cell Chem Biol 27, 409-419.Coutinho-Wolino, K.S., da Cruz, B.O., Cardozo, L., Fernandes, I.A., Mesquita, C.T., Stenvinkel, P., Bergman, P., Mafra, D., and Stockler-Pinto, M.B. (2022). Brazil nut supplementation does not affect trimethylamine-n-oxide plasma levels in patients with coronary artery disease. J Food Biochem, e14201.Crack, P.J., Taylor, J.M., Flentjar, N.J., de Haan, J., Hertzog, P., Iannello, R.C., and Kola, I. (2001). Increased infarct size and exacerbated apoptosis in the glutathione peroxidase-1 (Gpx-1) knockout mouse brain in response to ischemia/reperfusion injury. J Neurochem 78, 1389-1399.Cuartero, M.I., de la Parra, J., Perez-Ruiz, A., Bravo-Ferrer, I., Duran-Laforet, V., Garcia-Culebras, A., Garcia-Segura, J.M., Dhaliwal, J., Frankland, P.W., Lizasoain, I., et al. (2019). Abolition of aberrant neurogenesis ameliorates cognitive impairment after stroke in mice. J Clin Invest 129, 1536-1550.Curzon, P., Rustay, N.R., and Browman, K.E. (2009). Cued and Contextual Fear Conditioning for Rodents. Front Neurosci, 19-37.Dalla Via, A., Gargari, G., Taverniti, V., Rondini, G., Velardi, I., Gambaro, V., Visconti, G.L., De Vitis, V., Gardana, C., Ragg, E., et al. (2019). Urinary TMAO Levels Are Associated with the Taxonomic Composition of the Gut Microbiota and with the Choline TMA-Lyase Gene (cutC) Harbored by Enterobacteriaceae. Nutrients 12.Dalley, J.W., Cardinal, R.N., and Robbins, T.W. (2004). Prefrontal executive and cognitive functions in rodents: neural and neurochemical substrates. Neurosci Biobehav Rev 28, 771-784.Darsalia, V., Heldmann, U., Lindvall, O., and Kokaia, Z. (2005). Stroke-induced neurogenesis in aged brain. Stroke 36, 1790-1795.Dayer, A.G., Ford, A.A., Cleaver, K.M., Yassaee, M., and Cameron, H.A. (2003). Short-term and long-term survival of new neurons in the rat dentate gyrus. J Comp Neurol 460, 563-572.Deng, W., Aimone, J.B., and Gage, F.H. (2010). New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nat Rev Neurosci 11, 339-350.Denny, C.A., Burghardt, N.S., Schachter, D.M., Hen, R., and Drew, M.R. (2012). 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning. Hippocampus 22, 1188-1201.Dharmasaroja, P.A. (2016). Fluid Intake Related to Brain Edema in Acute Middle Cerebral Artery Infarction. Transl Stroke Res 7, 49-53.Dietrich, R.B., and Bradley, W.G., Jr. (1988). Iron accumulation in the basal ganglia following severe ischemic-anoxic insults in children. Radiology 168, 203-206.Dimkovikj, A., Fisher, B., Hutchison, K., and Van Hoewyk, D. (2015). Stuck between a ROS and a hard place: Analysis of the ubiquitin proteasome pathway in selenocysteine treated Brassica napus reveals different toxicities during selenium assimilation. J Plant Physiol 181, 50-54.Dixon, S.J., Lemberg, K.M., Lamprecht, M.R., Skouta, R., Zaitsev, E.M., Gleason, C.E., Patel, D.N., Bauer, A.J., Cantley, A.M., Yang, W.S., et al. (2012). Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149, 1060-1072.Doll, S., Freitas, F.P., Shah, R., Aldrovandi, M., da Silva, M.C., Ingold, I., Grocin, A.G., da Silva, T.N.X., Panzilius, E., Scheel, C.H., et al. (2019). FSP1 is a glutathione-independent ferroptosis suppressor. Nature 575, 693-+.Donovan, A., Lima, C.A., Pinkus, J.L., Pinkus, G.S., Zon, L.I., Robine, S., and Andrews, N.C. (2005). The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab 1, 191-200.Dorr, A., Sled, J.G., and Kabani, N. (2007). Three-dimensional cerebral vasculature of the CBA mouse brain: a magnetic resonance imaging and micro computed tomography study. Neuroimage 35, 1409-1423.Ehninger, D., and Kempermann, G. (2008). Neurogenesis in the adult hippocampus. Cell Tissue Res 331, 243-250.English, J.D., Yavagal, D.R., Gupta, R., Janardhan, V., Zaidat, O.O., Xavier, A.R., Nogueira, R.G., Kirmani, J.F., and Jovin, T.G. (2016). Mechanical Thrombectomy-Ready Comprehensive Stroke Center Requirements and Endovascular Stroke Systems of Care: Recommendations from the Endovascular Stroke Standards Committee of the Society of Vascular and Interventional Neurology (SVIN). Interv Neurol 4, 138-150.Erdemoglu, A.K., and Ozbakir, S. (2002). Serum ferritin levels and early prognosis of stroke. Eur J Neurol 9, 633-637.Eriksson, P.S., Perfilieva, E., Bjork-Eriksson, T., Alborn, A.M., Nordborg, C., Peterson, D.A., and Gage, F.H. (1998). Neurogenesis in the adult human hippocampus. Nat Med 4, 1313-1317.Esposito, E., Li, W., E, T.M., Park, J.H., Sencan, I., Guo, S., Shi, J., Lan, J., Lee, J., Hayakawa, K., et al. (2020). Potential circadian effects on translational failure for neuroprotection. Nature 582, 395-398.Faiz, M., Sachewsky, N., Gascon, S., Bang, K.W., Morshead, C.M., and Nagy, A. (2015). Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke. Cell Stem Cell 17, 624-634.Fang, K.M., Cheng, F.C., Huang, Y.L., Chung, S.Y., Jian, Z.Y., and Lin, M.C. (2013). Trace Element, Antioxidant Activity, and Lipid Peroxidation Levels in Brain Cortex of Gerbils After Cerebral Ischemic Injury. Biological Trace Element Research 152, 66-74.FAO, W. (2004). Vitamin and mineral requirements in human nutrition, Geneva. World Health Organization.Feng, H., Schorpp, K., Jin, J., Yozwiak, C.E., Hoffstrom, B.G., Decker, A.M., Rajbhandari, P., Stokes, M.E., Bender, H.G., Csuka, J.M., et al. (2020). Transferrin Receptor Is a Specific Ferroptosis Marker. Cell Rep 30, 3411-3423 e3417.Ferreira, R.L.U., Sena-Evangelista, K.C.M., de Azevedo, E.P., Pinheiro, F.I., Cobucci, R.N., and Pedrosa, L.F.C. (2021). Selenium in Human Health and Gut Microflora: Bioavailability of Selenocompounds and Relationship With Diseases. Front Nutr 8, 685317.Feustel, P.J., Ingvar, M.C., and Severinghaus, J.W. (1981). Cerebral oxygen availability and blood flow during middle cerebral artery occlusion: effects of pentobarbital. Stroke 12, 858-863.Fink, K., and Busch, H.J. (2019). Effect of selenium on early outcomes after cardiopulmonary resuscitation : A preliminary report from a retrospective data evaluation. Med Klin Intensivmed Notfmed 114, 246-251.Fishman, R.A. (1992). Cerebrospinal fluid in diseases of the nervous system (WB Saunders company).Fomenko, D.E., Marino, S.M., and Gladyshev, V.N. (2008). Functional diversity of cysteine residues in proteins and unique features of catalytic redox-active cysteines in thiol oxidoreductases. Mol Cells 26, 228-235.Fradejas, N., Serrano-Perez Mdel, C., Tranque, P., and Calvo, S. (2011). Selenoprotein S expression in reactive astrocytes following brain injury. Glia 59, 959-972.Friedmann Angeli, J.P., Schneider, M., Proneth, B., Tyurina, Y.Y., Tyurin, V.A., Hammond, V.J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014). Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat Cell Biol 16, 1180-1191.Frost, D.V., and Lish, P.M. (1975). Selenium in biology. Annu Rev Pharmacol 15, 259-284.Gage, F.H. (2019). Adult neurogenesis in mammals. Science 364, 827-828.Gao, M., Monian, P., Quadri, N., Ramasamy, R., and Jiang, X. (2015). Glutaminolysis and Transferrin Regulate Ferroptosis. Mol Cell 59, 298-308.Garcia-Yebenes, I., Garcia-Culebras, A., Pena-Martinez, C., Fernandez-Lopez, D., Diaz-Guzman, J., Negredo, P., Avendano, C., Castellanos, M., Gasull, T., Davalos, A., et al. (2018). Iron Overload Exacerbates the Risk of Hemorrhagic Transformation After tPA (Tissue-Type Plasminogen Activator) Administration in Thromboembolic Stroke Mice. Stroke 49, 2163-2172.Garcia-Yebenes, I., Sobrado, M., Moraga, A., Zarruk, J.G., Romera, V.G., Pradillo, J.M., de la Ossa, N.P., Moro, M.A., Davalos, A., and Lizasoain, I. (2012). Iron overload, measured as serum ferritin, increases brain damage induced by focal ischemia and early reperfusion. Neurochemistry International 61, 1364-1369.Ge, S., Yang, C.H., Hsu, K.S., Ming, G.L., and Song, H. (2007). A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54, 559-566.Geibig, C.S., Keiner, S., and Redecker, C. (2012). Functional recruitment of newborn hippocampal neurons after experimental stroke. Neurobiol Dis 46, 431-439.Gidday, J.M. (2006). Cerebral preconditioning and ischaemic tolerance. Nat Rev Neurosci 7, 437-448.Giraud, M., Cho, T.H., Nighoghossian, N., Maucort-Boulch, D., Deiana, G., Ostergaard, L., Baron, J.C., Fiehler, J., Pedraza, S., Derex, L., et al. (2015). Early Blood Brain Barrier Changes in Acute Ischemic Stroke: A Sequential MRI Study. J Neuroimaging 25, 959-963.Gotz, M., Sirko, S., Beckers, J., and Irmler, M. (2015). Reactive astrocytes as neural stem or progenitor cells: In vivo lineage, In vitro potential, and Genome-wide expression analysis. Glia 63, 1452-1468.Gould, E., Beylin, A., Tanapat, P., Reeves, A., and Shors, T.J. (1999). Learning enhances adult neurogenesis in the hippocampal formation. Nat Neurosci 2, 260-265.Goyal, M., Menon, B.K., van Zwam, W.H., Dippel, D.W., Mitchell, P.J., Demchuk, A.M., Davalos, A., Majoie, C.B., van der Lugt, A., de Miquel, M.A., et al. (2016). Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 387, 1723-1731.Griffiths, B.B., Ouyang, Y.-B., Xu, L., Sun, X., Giffard, R.G., and Stary, C.M. (2019). Post-injury inhibition of miR-181a promotes restoration of hippocampal CA1 neurons after transient forebrain ischemia in rats. eNeuro, ENEURO. 0002-0019.2019.Griffiths, N.M., Stewart, R.D., and Robinson, M.F. (1976). The metabolism of
[75Se]selenomethionine in four women. Br J Nutr 35, 373-382.Gronbaek, H., and Thorlacius-Ussing, O. (1992). Selenium in the central nervous system of rats exposed to 75-Se L-selenomethionine and sodium selenite. Biol Trace Elem Res 35, 119-127.Handy, D.E., Joseph, J., and Loscalzo, J. (2021). Selenium, a Micronutrient That Modulates Cardiovascular Health via Redox Enzymology. Nutrients 13.Harris, Z.L., Durley, A.P., Man, T.K., and Gitlin, J.D. (1999). Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. P Natl Acad Sci USA 96, 10812-10817.Haynes, W.G., and Webb, D.J. (1998). Endothelin as a regulator of cardiovascular function in health and disease. J Hypertens 16, 1081-1098.Health, A.I.o., and Welfare (2019). Deaths in Australia (Canberra: AIHW).Heyland, D.K., Dhaliwal, R., Suchner, U., and Berger, M.M. (2005). Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med 31, 327-337.Hill, K.E., Wu, S., Motley, A.K., Stevenson, T.D., Winfrey, V.P., Capecchi, M.R., Atkins, J.F., and Burk, R.F. (2012). Production of Selenoprotein P (Sepp1) by Hepatocytes Is Central to Selenium Homeostasis. Journal of Biological Chemistry 287, 40414-40424.Hill, K.E., Xia, Y., Akesson, B., Boeglin, M.E., and Burk, R.F. (1996). Selenoprotein P concentration in plasma is an index of selenium status in selenium-deficient and selenium-supplemented Chinese subjects. J Nutr 126, 138-145.Hodge, R.D., Bakken, T.E., Miller, J.A., Smith, K.A., Barkan, E.R., Graybuck, L.T., Close, J.L., Long, B., Johansen, N., Penn, O., et al. (2019). Conserved cell types with divergent features in human versus mouse cortex. Nature 573, 61-68.Hodge, R.D., Kahoud, R.J., and Hevner, R.F. (2012). Transcriptional control of glutamatergic differentiation during adult neurogenesis. Cell Mol Life Sci 69, 2125-2134.Homma, T., Kobayashi, S., Sato, H., and Fujii, J. (2019). Edaravone, a free radical scavenger, protects against ferroptotic cell death in vitro. Exp Cell Res 384, 111592.Hossmann, K.A. (2012). The two pathophysiologies of focal brain ischemia: implications for translational stroke research. J Cereb Blood Flow Metab 32, 1310-1316.Hou, S.T., Jiang, S.X., Desbois, A., Huang, D., Kelly, J., Tessier, L., Karchewski, L., and Kappler, J. (2006). Calpain-cleaved collapsin response mediator protein-3 induces neuronal death after glutamate toxicity and cerebral ischemia. J Neurosci 26, 2241-2249.Hou, S.T., Jiang, S.X., Zaharia, L.I., Han, X., Benson, C.L., Slinn, J., and Abrams, S.R. (2016). Phaseic Acid, an Endogenous and Reversible Inhibitor of Glutamate Receptors in Mouse Brain. J Biol Chem 291, 27007-27022.Houde, M., Desbiens, L., and D'Orleans-Juste, P. (2016). Endothelin-1: Biosynthesis, Signaling and Vasoreactivity. Adv Pharmacol 77, 143-175.Hu, H., Bi, C., Lin, T., Liu, L., Song, Y., Wang, B., Wang, P., Zhou, Z., Fang, C., Ma, H., et al. (2021). Sex difference in the association between plasma selenium and first stroke: a community-based nested case-control study. Biol Sex Differ 12, 39.Hu, X.F., Sharin, T., and Chan, H.M. (2017). Dietary and blood selenium are inversely associated with the prevalence of stroke among Inuit in Canada. J Trace Elem Med Biol 44, 322-330.Hu, X.F., Stranges, S., and Chan, L.H.M. (2019). Circulating Selenium Concentration Is Inversely Associated With the Prevalence of Stroke: Results From the Canadian Health Measures Survey and the National Health and Nutrition Examination Survey. J Am Heart Assoc 8, e012290.Hughes, P.M., Anthony, D.C., Ruddin, M., Botham, M.S., Rankine, E.L., Sablone, M., Baumann, D., Mir, A.K., and Perry, V.H. (2003). Focal lesions in the rat central nervous system induced by endothelin-1. J Neuropathol Exp Neurol 62, 1276-1286.Hurst, R., Armah, C.N., Dainty, J.R., Hart, D.J., Teucher, B., Goldson, A.J., Broadley, M.R., Motley, A.K., and Fairweather-Tait, S.J. (2010). Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr 91, 923-931.Iadecola, C., and Alexander, M. (2001). Cerebral ischemia and inflammation. Curr Opin Neurol 14, 89-94.Ide, S., Ide, K., Abe, K., Kobayashi, Y., Kitai, H., McKey, J., Strausser, S.A., O'Brien, L.L., Tata, A., Tata, P.R., et al. (2022). Sex differences in resilience to ferroptosis underlie sexual dimorphism in kidney injury and repair. Cell Rep 41, 111610.Imai, H., Hirao, F., Sakamoto, T., Sekine, K., Mizukura, Y., Saito, M., Kitamoto, T., Hayasaka, M., Hanaoka, K., and Nakagawa, Y. (2003). Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene. Biochem Biophys Res Commun 305, 278-286.Ingold, I., Berndt, C., Schmitt, S., Doll, S., Poschmann, G., Buday, K., Roveri, A., Peng, X., Porto Freitas, F., Seibt, T., et al. (2018). Selenium Utilization by GPX4 Is Required to Prevent Hydroperoxide-Induced Ferroptosis. Cell 172, 409-422 e421.Ishibashi, N., Prokopenko, O., Weisbrot-Lefkowitz, M., Reuhl, K.R., and Mirochnitchenko, O. (2002). Glutathione peroxidase inhibits cell death and glial activation following experimental stroke. Brain Res Mol Brain Res 109, 34-44.Jenkins, D.J.A., Kitts, D., Giovannucci, E.L., Sahye-Pudaruth, S., Paquette, M., Blanco Mejia, S., Patel, D., Kavanagh, M., Tsirakis, T., Kendall, C.W.C., et al. (2020). Selenium, antioxidants, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr.Jiang, S.X., Lertvorachon, J., Hou, S.T., Konishi, Y., Webster, J., Mealing, G., Brunette, E., Tauskela, J., and Preston, E. (2005). Chlortetracycline and demeclocycline inhibit calpains and protect mouse neurons against glutamate toxicity and cerebral ischemia. J Biol Chem 280, 33811-33818.Jin, K., Wang, X., Xie, L., Mao, X.O., and Greenberg, D.A. (2010). Transgenic ablation of doublecortin-expressing cells suppresses adult neurogenesis and worsens stroke outcome in mice. Proc Natl Acad Sci U S A 107, 7993-7998.Jin, K., Wang, X., Xie, L., Mao, X.O., Zhu, W., Wang, Y., Shen, J., Mao, Y., Banwait, S., and Greenberg, D.A. (2006). Evidence for stroke-induced neurogenesis in the human brain. Proc Natl Acad Sci U S A 103, 13198-13202.Jiwa, N.S., Garrard, P., and Hainsworth, A.H. (2010). Experimental models of vascular dementia and vascular cognitive impairment: a systematic review. J Neurochem 115, 814-828.Johnson, A., Varberg, Z., Benhardus, J., Maahs, A., and Schrater, P. (2012). The hippocampus and exploration: dynamically evolving behavior and neural representations. Front Hum Neurosci 6, 216.Ju, W., Li, X., Li, Z., Wu, G.R., Fu, X.F., Yang, X.M., Zhang, X.Q., and Gao, X.B. (2017). The effect of selenium supplementation on coronary heart disease: A systematic review and meta-analysis of randomized controlled trials. J Trace Elem Med Biol 44, 8-16.Kalra, L., Irshad, S., Hodsoll, J., Simpson, M., Gulliford, M., Smithard, D., Patel, A., Rebollo-Mesa, I., and Investigators, S.-I. (2015). Prophylactic antibiotics after acute stroke for reducing pneumonia in patients with dysphagia (STROKE-INF): a prospective, cluster-randomised, open-label, masked endpoint, controlled clinical trial. Lancet 386, 1835-1844.Kehrer, J.P. (2000). The Haber-Weiss reaction and mechanisms of toxicity. Toxicology 149, 43-50.Kempermann, G., Gage, F.H., Aigner, L., Song, H., Curtis, M.A., Thuret, S., Kuhn, H.G., Jessberger, S., Frankland, P.W., Cameron, H.A., et al. (2018). Human Adult Neurogenesis: Evidence and Remaining Questions. Cell Stem Cell 23, 25-30.Kempermann, G., Jessberger, S., Steiner, B., and Kronenberg, G. (2004). Milestones of neuronal development in the adult hippocampus. Trends in Neurosciences 27, 447-452.Kempermann, G., Kuhn, H.G., and Gage, F.H. (1998). Experience-induced neurogenesis in the senescent dentate gyrus. Journal of Neuroscience 18, 3206-3212.Kenny, E.M., Fidan, E., Yang, Q., Anthonymuthu, T.S., New, L.A., Meyer, E.A., Wang, H., Kochanek, P.M., Dixon, C.E., Kagan, V.E., et al. (2019). Ferroptosis Contributes to Neuronal Death and Functional Outcome After Traumatic Brain Injury. Crit Care Med 47, 410-418.Khan, H.A. (2010). Selenium partially reverses the depletion of striatal dopamine and its metabolites in MPTP-treated C57BL mice. Neurochem Int 57, 489-491.Khan, M.B., Hoda, M.N., Ishrat, T., Ahmad, S., Moshahid Khan, M., Ahmad, A., Yusuf, S., and Islam, F. (2012). Neuroprotective efficacy of Nardostachys jatamansi and crocetin in conjunction with selenium in cognitive impairment. Neurol Sci 33, 1011-1020.Kieliszek, M., and Blazejak, S. (2013). Selenium: Significance, and outlook for supplementation. Nutrition 29, 713-718.Kilkenny, C., Browne, W.J., Cuthill, I.C., Emerson, M., and Altman, D.G. (2010). Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8, e1000412.Kim, M., Byun, J., Chung, Y., Lee, S.U., Park, J.E., Park, W., Park, J.C., Ahn, J.S., and Lee, S. (2021). Reactive Oxygen Species Scavenger in Acute Intracerebral Hemorrhage Patients: A Multicenter, Randomized Controlled Trial. Stroke 52, 1172-1181.Kirby, E.D., Friedman, A.R., Covarrubias, D., Ying, C., Sun, W.G., Goosens, K.A., Sapolsky, R.M., and Kaufer, D. (2012). Basolateral amygdala regulation of adult hippocampal neurogenesis and fear-related activation of newborn neurons. Mol Psychiatry 17, 527-536.Kobayashi, S., Fukuma, S., Ikenoue, T., Fukuhara, S., and Kobayashi, S. (2019). Effect of Edaravone on Neurological Symptoms in Real-World Patients With Acute Ischemic Stroke. Stroke 50, 1805-1811.Kojima, T., Hirota, Y., Ema, M., Takahashi, S., Miyoshi, I., Okano, H., and Sawamoto, K. (2010). Subventricular Zone-Derived Neural Progenitor Cells Migrate Along a Blood Vessel Scaffold Toward the Post-stroke Striatum. Stem Cells 28, 545-554.Kokaia, Z., Thored, P., Arvidsson, A., and Lindvall, O. (2006). Regulation of stroke-induced neurogenesis in adult brain--recent scientific progress. Cereb Cortex 16 Suppl 1, i162-167.Koyama, H., Abdulah, R., Ohkubo, T., Imai, Y., Satoh, H., and Nagai, K. (2009). Depressed serum selenoprotein P: possible new predicator of increased risk for cerebrovascular events. Nutr Res 29, 94-99.Kryukov, G.V., Castellano, S., Novoselov, S.V., Lobanov, A.V., Zehtab, O., Guigo, R., and Gladyshev, V.N. (2003). Characterization of mammalian selenoproteomes. Science 300, 1439-1443.Kryukov, G.V., and Gladyshev, V.N. (2000). Selenium metabolism in zebrafish: multiplicity of selenoprotein genes and expression of a protein containing 17 selenocysteine residues. Genes Cells 5, 1049-1060.Kuhbacher, M., Bartel, J., Hoppe, B., Alber, D., Bukalis, G., Brauer, A.U., Behne, D., and Kyriakopoulos, A. (2009). The brain selenoproteome: priorities in the hierarchy and different levels of selenium homeostasis in the brain of selenium-deficient rats. J Neurochem 110, 133-142.Kuhn, H.G., Dickinson-Anson, H., and Gage, F.H. (1996). Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16, 2027-2033.Kumar, S., Selim, M.H., and Caplan, L.R. (2010). Medical complications after stroke. Lancet Neurol 9, 105-118.Kurita, N., Yamashiro, K., Kuroki, T., Tanaka, R., Urabe, T., Ueno, Y., Miyamoto, N., Takanashi, M., Shimura, H., Inaba, T., et al. (2020). Metabolic endotoxemia promotes neuroinflammation after focal cerebral ischemia. J Cereb Blood Flow Metab 40, 2505-2520.Kuroiwa, T., Ting, P., Martinez, H., and Klatzo, I. (1985). The Biphasic Opening of the Blood-Brain-Barrier to Proteins Following Temporary Middle Cerebral-Artery Occlusion. Acta Neuropathol 68, 122-129.Kutuk, S.G., and Naziroglu, M. (2020). Selenium Diminishes Docetaxel-Induced Cell Death, Oxidative Stress, and Inflammation in the Laryngotracheal Epithelium of the Mouse. Biol Trace Elem Res 196, 184-194.Lai, T.W., Zhang, S., and Wang, Y.T. (2014). Excitotoxicity and stroke: identifying novel targets for neuroprotection. Prog Neurobiol 115, 157-188.Lakomkin, N., Dhamoon, M., Carroll, K., Singh, I.P., Tuhrim, S., Lee, J., Fifi, J.T., and Mocco, J. (2019). Prevalence of large vessel occlusion in patients presenting with acute ischemic stroke: a 10-year systematic review of the literature. J Neurointerv Surg 11, 241-245.Lambertsen, K.L., Finsen, B., and Clausen, B.H. (2019). Post-stroke inflammation-target or tool for therapy? Acta Neuropathol 137, 693-714.Langdon, K.D., Maclellan, C.L., and Corbett, D. (2010). Prolonged, 24-h delayed peripheral inflammation increases short- and long-term functional impairment and histopathological damage after focal ischemia in the rat. J Cereb Blood Flow Metab 30, 1450-1459.Leiter, O., Zhuo, Z., Rust, R., Wasielewska, J.M., Gronnert, L., Kowal, S., Overall, R.W., Adusumilli, V.S., Blackmore, D.G., Southon, A., et al. (2022). Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging. Cell Metab 34, 408-423 e408.Leker, R.R., Soldner, F., Velasco, I., Gavin, D.K., Androutsellis-Theotokis, A., and McKay, R.D.G. (2007). Long-lasting regeneration after ischemia in the cerebral cortex. Stroke 38, 153-161.Letavayova, L., Vlckova, V., and Brozmanova, J. (2006). Selenium: from cancer prevention to DNA damage. Toxicology 227, 1-14.Leuner, B., Kozorovitskiy, Y., Gross, C.G., and Gould, E. (2007). Diminished adult neurogenesis in the marmoset brain precedes old age. P Natl Acad Sci USA 104, 17169-17173.Lichtenwalner, R.J., and Parent, J.M. (2006). Adult neurogenesis and the ischemic forebrain. J Cereb Blood Flow Metab 26, 1-20.Lipscomb, D.C., Gorman, L.G., Traystman, R.J., and Hurn, P.D. (1998). Low molecular weight iron in cerebral ischemic acidosis in vivo. Stroke 29, 487-492.Liu, J., Solway, K., Messing, R.O., and Sharp, F.R. (1998). Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci 18, 7768-7778.Liu, L., Huang, W., Wang, J., Song, H., Cen, J., and Ji, B. (2017). Anthraquinone derivative exerted hormetic effect on the apoptosis in oxygen-glucose deprivation-induced PC12 cells via ERK and Akt activated Nrf2/HO-1 signaling pathway. Chem Biol Interact 262, 1-11.Liu, X.S., Zhang, Z.G., Zhang, R.L., Gregg, S., Morris, D.C., Wang, Y., and Chopp, M. (2007). Stroke induces gene profile changes associated with neurogenesis and angiogenesis in adult subventricular zone progenitor cells. J Cereb Blood Flow Metab 27, 564-574.Lo, E.H., Moskowitz, M.A., and Jacobs, T.P. (2005). Exciting, radical, suicidal: how brain cells die after stroke. Stroke 36, 189-192.Luna, V.M., Anacker, C., Burghardt, N.S., Khandaker, H., Andreu, V., Millette, A., Leary, P., Ravenelle, R., Jimenez, J.C., Mastrodonato, A., et al. (2019). Adult-born hippocampal neurons bidirectionally modulate entorhinal inputs into the dentate gyrus. Science 364, 578-583.Lunardi Baccetto, S., and Lehmann, C. (2019). Microcirculatory Changes in Experimental Models of Stroke and CNS-Injury Induced Immunodepression. Int J Mol Sci 20.Luo, C.X., Jiang, J., Zhou, Q.G., Zhu, X.J., Wang, W., Zhang, Z.J., Han, X., and Zhu, D.Y. (2007). Voluntary exercise-induced neurogenesis in the postischemic dentate gyrus is associated with spatial memory recovery from stroke. Journal of Neuroscience Research 85, 1637-1646.Lv, Q., Liang, X., Nong, K., Gong, Z., Qin, T., Qin, X., Wang, D., and Zhu, Y. (2021). Advances in Research on the Toxicological Effects of Selenium. Bull Environ Contam Toxicol 106, 715-726.MacFarquhar, J.K., Broussard, D.L., Melstrom, P., Hutchinson, R., Wolkin, A., Martin, C., Burk, R.F., Dunn, J.R., Green, A.L., Hammond, R., et al. (2010). Acute selenium toxicity associated with a dietary supplement. Arch Intern Med 170, 256-261.Magnusson, J.P., Goritz, C., Tatarishvili, J., Dias, D.O., Smith, E.M.K., Lindvall, O., Kokaia, Z., and Frisen, J. (2014). A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse. Science 346, 237-241.Mamtilahun, M., Jiang, L., Song, Y., Shi, X., Liu, C., Jiang, Y., Deng, L., Zheng, H., Shen, H., Li, Y., et al. (2021). Plasma from healthy donors protects blood-brain barrier integrity via FGF21 and improves the recovery in a mouse model of cerebral ischaemia. Stroke Vasc Neurol.Manzanares, W., Langlois, P.L., and Heyland, D.K. (2015). Pharmaconutrition with selenium in critically ill patients: what do we know? Nutr Clin Pract 30, 34-43.Markovic, J., Borras, C., Ortega, A., Sastre, J., Vina, J., and Pallardo, F.V. (2007). Glutathione is recruited into the nucleus in early phases of cell proliferation. J Biol Chem 282, 20416-20424.Marler, J.R., Brott, T., Broderick, J., Kothari, R., Odonoghue, M., Barsan, W., Tomsick, T., Spilker, J., Miller, R., Sauerbeck, L., et al. (1995). Tissue-Plasminogen Activator for Acute Ischemic Stroke. New Engl J Med 333, 1581-1587.Massey, P.V., Warburton, E.C., Wynick, D., Brown, M.W., and Bashir, Z.I. (2003). Galanin regulates spatial memory but not visual recognition memory or synaptic plasticity in perirhinal cortex. Neuropharmacology 44, 40-48.Mehta, S.L., Kumari, S., Mendelev, N., and Li, P.A. (2012). Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia. BMC Neurosci 13, 79.Merali, Z., Huang, K., Mikulis, D., Silver, F., and Kassner, A. (2017). Evolution of blood-brain-barrier permeability after acute ischemic stroke. PLoS One 12, e0171558.Mézes, M., and Balogh, K. (2009). Prooxidant mechanisms of selenium toxicity–a review. Acta Biologica Szegediensis 53, 15-18.Mirończuk, A., Kapica-Topczewska, K., Socha, K., Soroczyńska, J., Jamiołkowski, J., Kułakowska, A., and Kochanowicz, J. (2021). Selenium, Copper, Zinc Concentrations and Cu/Zn, Cu/Se Molar Ratios in the Serum of Patients with Acute Ischemic Stroke in Northeastern Poland—A New Insight into Stroke Pathophysiology. Nutrients 13, 2139.Moreno-Jiménez, E.P., Flor-García, M., Terreros-Roncal, J., Rábano, A., Cafini, F., Pallas-Bazarra, N., Ávila, J., and Llorens-Martín, M. (2019). Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat Med 25, 554-560.Moretti, A., Ferrari, F., and Villa, R.F. (2015). Neuroprotection for ischaemic stroke: current status and challenges. Pharmacol Ther 146, 23-34.Morita-Fujimura, Y., Fujimura, M., Yoshimoto, T., and Chan, P.H. (2001). Superoxide during reperfusion contributes to caspase-8 expression and apoptosis after transient focal stroke. Stroke 32, 2356-2361.Mortality, G.B.D., and Causes of Death, C. (2016). Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1459-1544.Moskowitz, M.A., Lo, E.H., and Iadecola, C. (2010). The science of stroke: mechanisms in search of treatments. Neuron 67, 181-198.Nedergaard, M., Kraig, R.P., Tanabe, J., and Pulsinelli, W.A. (1991). Dynamics of Interstitial and Intracellular Ph in Evolving Brain Infarct. Am J Physiol 260, R581-R588.Nelson, M.A., Porterfield, B.W., Jacobs, E.T., and Clark, L.C. (1999). Selenium and prostate cancer prevention. Semin Urol Oncol 17, 91-96.Nie, J., Xie, L., Zhao, B.X., Li, Y., Qiu, B., Zhu, F., Li, G.F., He, M., Wang, Y., Wang, B., et al. (2018). Serum Trimethylamine N-Oxide Concentration Is Positively Associated With First Stroke in Hypertensive Patients. Stroke 49, 2021-2028.Niv, F., Keiner, S., Krishna, Witte, O.W., Lie, D.C., and Redecker, C. (2012). Aberrant neurogenesis after stroke: a retroviral cell labeling study. Stroke 43, 2468-2475.Nogueira, R.G., Jadhav, A.P., Haussen, D.C., Bonafe, A., Budzik, R.F., Bhuva, P., Yavagal, D.R., Ribo, M., Cognard, C., Hanel, R.A., et al. (2018). Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med 378, 11-21.O'Collins, V.E., Macleod, M.R., Donnan, G.A., Horky, L.L., van der Worp, B.H., and Howells, D.W. (2006). 1,026 experimental treatments in acute stroke. Ann Neurol 59, 467-477.Ohab, J.J., Fleming, S., Blesch, A., and Carmichael, S.T. (2006). A neurovascular niche for neurogenesis after stroke. J Neurosci 26, 13007-13016.Olson, G.E., Winfrey, V.P., Nagdas, S.K., Hill, K.E., and Burk, R.F. (2007). Apolipoprotein E receptor-2 (ApoER2) mediates selenium uptake from selenoprotein P by the mouse testis. J Biol Chem 282, 12290-12297.Olson, O.E., and Palmer, I.S. (1976). Selenoamino acids in tissues of rats administered inorganic selenium. Metabolism 25, 299-306.Organization, W.H. (2004). Guidelines for drinking-water quality, Vol 1 (World Health Organization).Ornoy, A., Rand, S.B., and Bischitz, N. (2010). Hyperglycemia and hypoxia are interrelated in their teratogenic mechanism: studies on cultured rat embryos. Birth Defects Res B Dev Reprod Toxicol 89, 106-115.Oster, O., Schmiedel, G., and Prellwitz, W. (1988). The organ distribution of selenium in German adults. Biol Trace Elem Res 15, 23-45.Ostrakhovitch, E.A., and Semenikhin, O.A. (2013). The role of redox environment in neurogenic development. Arch Biochem Biophys 534, 44-54.Ozbal, S., Erbil, G., Kocdor, H., Tugyan, K., Pekcetin, C., and Ozogul, C. (2008). The effects of selenium against cerebral ischemia-reperfusion injury in rats. Neurosci Lett 438, 265-269.Palmer, C., Menzies, S.L., Roberts, R.L., Pavlick, G., and Connor, J.R. (1999). Changes in iron histochemistry after hypoxic-ischemic brain injury in the neonatal rat (vol 56, pg 60, 1999). Journal of Neuroscience Research 58, 349-355.Parent, J.M., and Lowenstein, D.H. (2002). Seizure-induced neurogenesis: are more new neurons good for an adult brain? Prog Brain Res 135, 121-131.Parent, J.M., Vexler, Z.S., Gong, C., Derugin, N., and Ferriero, D.M. (2002). Rat forebrain neurogenesis and striatal neuron replacement after focal stroke. Ann Neurol 52, 802-813.Parnham, M.J., and Sies, H. (2013). The early research and development of ebselen. Biochem Pharmacol 86, 1248-1253.Patt, A., Horesh, I.R., Berger, E.M., Harken, A.H., and Repine, J.E. (1990). Iron depletion or chelation reduces ischemia/reperfusion-induced edema in gerbil brains. J Pediatr Surg 25, 224-227; discussion 227-228.Paxinos, G., and Franklin, K. (2012). The Mouse Brain in Stereotaxic Coordinates 2nd edn, 52–54 (Academic Press).Peh, A., O'Donnell, J.A., Broughton, B.R.S., and Marques, F.Z. (2022). Gut Microbiota and Their Metabolites in Stroke: A Double-Edged Sword. Stroke 53, 1788-1801.Percie du Sert, N., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., Dirnagl, U., Emerson, M., et al. (2020). Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol 18, e3000411.Persson-Moschos, M., Huang, W., Srikumar, T.S., Akesson, B., and Lindeberg, S. (1995). Selenoprotein P in serum as a biochemical marker of selenium status. Analyst 120, 833-836.Pillai, R., Uyehara-Lock, J.H., and Bellinger, F.P. (2014). Selenium and selenoprotein function in brain disorders. IUBMB Life 66, 229-239.Pilz, G.A., Bottes, S., Betizeau, M., Jorg, D.J., Carta, S., Simons, B.D., Helmchen, F., and Jessberger, S. (2018). Live imaging of neurogenesis in the adult mouse hippocampus. Science 359, 658-662.Pinault, D. (2004). The thalamic reticular nucleus: structure, function and concept. Brain Res Brain Res Rev 46, 1-31.Pitts, M.W., Byrns, C.N., Ogawa-Wong, A.N., Kremer, P., and Berry, M.J. (2014). Selenoproteins in nervous system development and function. Biol Trace Elem Res 161, 231-245.Plummer, J.D., Postnikoff, S.D., Tyler, J.K., and Johnson, J.E. (2021). Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice. Elife 10.Povysheva, N., Nigam, A., Brisbin, A.K., Johnson, J.W., and Barrionuevo, G. (2019). Oxygen-Glucose Deprivation Differentially Affects Neocortical Pyramidal Neurons and Parvalbumin-Positive Interneurons. Neuroscience 412, 72-82.Powers, W.J., Derdeyn, C.P., Biller, J., Coffey, C.S., Hoh, B.L., Jauch, E.C., Johnston, K.C., Johnston, S.C., Khalessi, A.A., Kidwell, C.S., et al. (2015). 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 46, 3020-3035.Powers, W.J., Rabinstein, A.A., Ackerson, T., Adeoye, O.M., Bambakidis, N.C., Becker, K., Biller, J., Brown, M., Demaerschalk, B.M., Hoh, B., et al. (2018). 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 49, E46-E110.Prass, K., Ruscher, K., Karsch, M., Isaev, N., Megow, D., Priller, J., Scharff, A., Dirnagl, U., and Meisel, A. (2002). Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro. J Cereb Blood Flow Metab 22, 520-525.Qian, Z.M., and Shen, X. (2001). Brain iron transport and neurodegeneration. Trends Mol Med 7, 103-108.Raber, J., Fan, Y., Matsumori, Y., Liu, Z.Y., Weinstein, P.R., Fike, J.R., and Liu, J.L. (2004). Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits. Annals of Neurology 55, 381-389.Rayman, M.P., Winther, K.H., Pastor-Barriuso, R., Cold, F., Thvilum, M., Stranges, S., Guallar, E., and Cold, S. (2018). Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomised controlled trial. Free Radical Bio Med 127, 46-54.Reisinger, J., Hollinger, K., Lang, W., Steiner, C., Winter, T., Winter, A., Mori, M., Lindorfer, A., Kiblbock, D., and Siostrzonek, P. (2009). Does early administration of selenium improve neurological outcome after cardiac arrest? Am J Emerg Med 27, 176-181.Ren, B., Wang, L., Shi, L., Jin, X., Liu, Y., Liu, R.H., Yin, F., Cadenas, E., Dai, X., Liu, Z., et al. (2021). Methionine restriction alleviates age-associated cognitive decline via fibroblast growth factor 21. Redox Biol 41, 101940.Rennert, R.C., Wali, A.R., Steinberg, J.A., Santiago-Dieppa, D.R., Olson, S.E., Pannell, J.S., and Khalessi, A.A. (2019). Epidemiology, Natural History, and Clinical Presentation of Large Vessel Ischemic Stroke. Neurosurgery 85, S4-S8.Rexidamu, M., Li, H., Jin, H., and Huang, J. (2019). Serum levels of Trimethylamine-N-oxide in patients with ischemic stroke. Biosci Rep 39.Roman, M., Jitaru, P., and Barbante, C. (2014). Selenium biochemistry and its role for human health. Metallomics 6, 25-54.Roome, R.B., Bartlett, R.F., Jeffers, M., Xiong, J., Corbett, D., and Vanderluit, J.L. (2014). A reproducible Endothelin-1 model of forelimb motor cortex stroke in the mouse. J Neurosci Methods 233, 34-44.Roy, D.S., Arons, A., Mitchell, T.I., Pignatelli, M., Ryan, T.J., and Tonegawa, S. (2016). Memory retrieval by activating engram cells in mouse models of early Alzheimer's disease. Nature 531, 508-512.Rozyczka, J., Figiel, M., and Engele, J. (2004). Endothelins negatively regulate glial glutamate transporter expression. Brain Pathol 14, 406-414.Sahai, S. (1990). Glutamate in the mammalian CNS. Eur Arch Psychiatry Clin Neurosci 240, 121-133.Salimian, M., Soleimani, A., Bahmani, F., Tabatabaei, S.M.H., Asemi, Z., and Talari, H.R. (2022). The effects of selenium administration on carotid intima-media thickness and metabolic status in diabetic hemodialysis patients: A randomized, double-blind, placebo-controlled trial. Clin Nutr ESPEN 47, 58-62.Salonen, J.T., Salonen, R., Seppanen, K., Kantola, M., Parviainen, M., Alfthan, G., Maenpaa, P.H., Taskinen, E., and Rauramaa, R. (1988). Relationship of Serum Selenium and Antioxidants to Plasma-Lipoproteins, Platelet Aggregability and Prevalent Ischemic Heart-Disease in Eastern Finnish Men. Atherosclerosis 70, 155-160.Samuni, Y., Goldstein, S., Dean, O.M., and Berk, M. (2013). The chemistry and biological activities of N-acetylcysteine. Biochim Biophys Acta 1830, 4117-4129.Sanchez-Bezanilla, S., Hood, R.J., Collins-Praino, L.E., Turner, R.J., Walker, F.R., Nilsson, M., and Ong, L.K. (2021). More than motor impairment: A spatiotemporal analysis of cognitive impairment and associated neuropathological changes following cortical photothrombotic stroke. J Cereb Blood Flow Metab, 271678X211005877.Sandoval, K.E., and Witt, K.A. (2008). Blood-brain barrier tight junction permeability and ischemic stroke. Neurobiology of disease 32, 200-219.Sarraj, A., Hassan, A.E., Savitz, S., Sitton, C., Grotta, J., Chen, P., Cai, C., Cutter, G., Imam, B., Reddy, S., et al. (2019). Outcomes of Endovascular Thrombectomy vs Medical Management Alone in Patients With Large Ischemic Cores: A Secondary Analysis of the Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT) Study. JAMA Neurol.Sato, H., Tamba, M., Okuno, S., Sato, K., Keino-Masu, K., Masu, M., and Bannai, S. (2002). Distribution of cystine/glutamate exchange transporter, system x(c)-, in the mouse brain. J Neurosci 22, 8028-8033.Schirrmacher, R., Dea, M., Heiss, W.D., Kostikov, A., Funck, T., Quessy, S., Bedell, B., Dancause, N., and Thiel, A. (2016). Which Aspects of Stroke Do Animal Models Capture? A Multitracer Micro-PET Study of Focal Ischemia with Endothelin-1. Cerebrovasc Dis 41, 139-147.Schneider, C., Okun, J.G., Schwarz, K.V., Hauke, J., Zorn, M., Nürnberg, C., Ungerer, M., Ringleb, P.A., and Mundiyanapurath, S. (2020). Trimethylamine-N-oxide is elevated in the acute phase after ischaemic stroke and decreases within the first days. Eur J Neurol 27, 1596-1603.Schoenfeld, T.J., Rada, P., Pieruzzini, P.R., Hsueh, B., and Gould, E. (2013). Physical exercise prevents stress-induced activation of granule neurons and enhances local inhibitory mechanisms in the dentate gyrus. J Neurosci 33, 7770-7777.Schrauzer, G.N. (2000). Selenomethionine: a review of its nutritional significance, metabolism and toxicity. J Nutr 130, 1653-1656.Seiler, A., Schneider, M., Forster, H., Roth, S., Wirth, E.K., Culmsee, C., Plesnila, N., Kremmer, E., Radmark, O., Wurst, W., et al. (2008). Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 8, 237-248.Seners, P., Turc, G., Maier, B., Mas, J.L., Oppenheim, C., and Baron, J.C. (2016). Incidence and Predictors of Early Recanalization After Intravenous Thrombolysis: A Systematic Review and Meta-Analysis. Stroke 47, 2409-2412.Shahar, A., Patel, K.V., Semba, R.D., Bandinelli, S., Shahar, D.R., Ferrucci, L., and Guralnik, J.M. (2010). Plasma Selenium is Positively Related to Performance in Neurological Tasks Assessing Coordination and Motor Speed. Movement Disord 25, 1909-1915.Sharkey, J., Ritchie, I.M., and Kelly, P.A. (1993). Perivascular microapplication of endothelin-1: a new model of focal cerebral ischaemia in the rat. J Cereb Blood Flow Metab 13, 865-871.Sharma, A.K., and Amin, S. (2013). Post SELECT: selenium on trial. Future Med Chem 5, 163-174.Shi, K., Tian, D.C., Li, Z.G., Ducruet, A.F., Lawton, M.T., and Shi, F.D. (2019). Global brain inflammation in stroke. Lancet Neurol 18, 1058-1066.Shi, W., Su, L., Wang, J., Wang, F., Liu, X., and Dou, J. (2022). Correlation between dietary selenium intake and stroke in the National Health and Nutrition Examination Survey 2003-2018. Ann Med 54, 1395-1402.Shih, A.Y., Erb, H., Sun, X., Toda, S., Kalivas, P.W., and Murphy, T.H. (2006). Cystine/glutamate exchange modulates glutathione supply for neuroprotection from oxidative stress and cell proliferation. J Neurosci 26, 10514-10523.Shivakumar, B.R., Kolluri, S.V., and Ravindranath, V. (1995). Glutathione and protein thiol homeostasis in brain during reperfusion after cerebral ischemia. J Pharmacol Exp Ther 274, 1167-1173.Sierra, A., Encinas, J.M., Deudero, J.J.P., Chancey, J.H., Enikolopov, G., Overstreet-Wadiche, L.S., Tsirka, S.E., and Maletic-Savatic, M. (2010). Microglia Shape Adult Hippocampal Neurogenesis through Apoptosis-Coupled Phagocytosis. Cell Stem Cell 7, 483-495.Sies, H., Sharov, V.S., Klotz, L.O., and Briviba, K. (1997). Glutathione peroxidase protects against peroxynitrite-mediated oxidations. A new function for selenoproteins as peroxynitrite reductase. J Biol Chem 272, 27812-27817.Siesjo, B.K., Katsura, K., and Kristian, T. (1996). Acidosis-related damage. Adv Neurol 71, 209-236.Simon, R.P., Benowitz, N., Hedlund, R., and Copeland, J. (1985). Influence of the Blood-Brain Ph Gradient on Brain Phenobarbital Uptake during Status Epilepticus. J Pharmacol Exp Ther 234, 830-835.Smith, M., and Westfall, B. (1937). Further field studies on the selenium problem in relation to public health. Public Health Reports (1896-1970), 1375-1384.Smith, W.S., Lev, M.H., English, J.D., Camargo, E.C., Chou, M., Johnston, S.C., Gonzalez, G., Schaefer, P.W., Dillon, W.P., Koroshetz, W.J., et al. (2009). Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA. Stroke 40, 3834-3840.Soda, K., Oikawa, T., and Esaki, N. (1999). Vitamin B6 enzymes participating in selenium amino acid metabolism. Biofactors 10, 257-262.Song, G.L., Zhang, Z.H., Wen, L., Chen, C., Shi, Q.X., Zhang, Y., Ni, J.Z., and Liu, Q. (2014). Selenomethionine Ameliorates Cognitive Decline, Reduces Tau Hyperphosphorylation, and Reverses Synaptic Deficit in the Triple Transgenic Mouse Model of Alzheimer's Disease. Journal of Alzheimers Disease 41, 85-99.Sorrells, S.F., Paredes, M.F., Cebrian-Silla, A., Sandoval, K., Qi, D., Kelley, K.W., James, D., Mayer, S., Chang, J., Auguste, K.I., et al. (2018). Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 555, 377-381.Sorrells, S.F., Paredes, M.F., Zhang, Z., Kang, G., Pastor-Alonso, O., Biagiotti, S., Page, C.E., Sandoval, K., Knox, A., Connolly, A., et al. (2021). Positive Controls in Adults and Children Support That Very Few, If Any, New Neurons Are Born in the Adult Human Hippocampus. J Neurosci 41, 2554-2565.Sozmen, E.G., Kolekar, A., Havton, L.A., and Carmichael, S.T. (2009). A white matter stroke model in the mouse: axonal damage, progenitor responses and MRI correlates. J Neurosci Methods 180, 261-272.Spalding, K.L., Bergmann, O., Alkass, K., Bernard, S., Salehpour, M., Huttner, H.B., Bostrom, E., Westerlund, I., Vial, C., Buchholz, B.A., et al. (2013). Dynamics of hippocampal neurogenesis in adult humans. Cell 153, 1219-1227.Spallholz, J. (1987). Nutritional, chemical, and toxicological evaluation of a high-selenium yeast. Selenium in Biology and Medicine, 516-529.Spallholz, J.E. (1994). On the nature of selenium toxicity and carcinostatic activity. Free Radic Biol Med 17, 45-64.Steinert, P., Bachner, D., and Flohe, L. (1998). Analysis of the mouse selenoprotein P gene. Biol Chem 379, 683-691.Stewart, R.D., Griffiths, N.M., Thomson, C.D., and Robinson, M.F. (1978). Quantitative selenium metabolism in normal New Zealand women. Br J Nutr 40, 45-54.Stockwell, B.R., Friedmann Angeli, J.P., Bayir, H., Bush, A.I., Conrad, M., Dixon, S.J., Fulda, S., Gascon, S., Hatzios, S.K., Kagan, V.E., et al. (2017). Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell 171, 273-285.Stokum, J.A., Gerzanich, V., and Simard, J.M. (2016). Molecular pathophysiology of cerebral edema. J Cerebr Blood F Met 36, 513-538.Stone, S.S., Teixeira, C.M., Devito, L.M., Zaslavsky, K., Josselyn, S.A., Lozano, A.M., and Frankland, P.W. (2011). Stimulation of entorhinal cortex promotes adult neurogenesis and facilitates spatial memory. J Neurosci 31, 13469-13484.Sun, C.R., Sun, H., Wu, S., Lee, C.C., Akamatsu, Y., Wang, R.K.K., Kernie, S.G., and Liu, J.L. (2013). Conditional Ablation of Neuroprogenitor Cells in Adult Mice Impedes Recovery of Poststroke Cognitive Function and Reduces Synaptic Connectivity in the Perforant Pathway. Journal of Neuroscience 33, 17314-17325.Sun, D., Daniels, T.E., Rolfe, A., Waters, M., and Hamm, R. (2015). Inhibition of injury-induced cell proliferation in the dentate gyrus of the hippocampus impairs spontaneous cognitive recovery after traumatic brain injury. J Neurotrauma 32, 495-505.Takei, Y. (2019). Age-dependent decline in neurogenesis of the hippocampus and extracellular nucleotides. Hum Cell 32, 88-94.Tang, C., Wang, M., Wang, P., Wang, L., Wu, Q., and Guo, W. (2019). Neural Stem Cells Behave as a Functional Niche for the Maturation of Newborn Neurons through the Secretion of PTN. Neuron 101, 32-44 e36.Tang, H.D., Wang, Y.M., Xie, L., Mao, X.O., Won, S.J., Galvan, V., and Jin, K.L. (2009). Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia. Neurobiol Aging 30, 299-308.Tannenholz, L., Hen, R., and Kheirbek, M.A. (2016). GluN2B-Containg NMDA Receptors on Adult-Born Granule Cells Contribute to the Antidepressant Action of Fluoxetine. Front Neurosci 10, 242.Tenorio, M., Graciliano, N.G., Moura, F.A., Oliveira, A.C.M., and Goulart, M.O.F. (2021). N-Acetylcysteine (NAC): Impacts on Human Health. Antioxidants (Basel) 10.Terreros-Roncal, J., Moreno-Jimenez, E.P., Flor-Garcia, M., Rodriguez-Moreno, C.B., Trinchero, M.F., Cafini, F., Rabano, A., and Llorens-Martin, M. (2021). Impact of neurodegenerative diseases on human adult hippocampal neurogenesis. Science 374, 1106-1113.Thomalla, G., Simonsen, C.Z., Boutitie, F., Andersen, G., Berthezene, Y., Cheng, B., Cheripelli, B., Cho, T.H., Fazekas, F., Fiehler, J., et al. (2018). MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med 379, 611-622.Thomas, M., Nicklee, T., and Hedley, D.W. (1995). Differential effects of depleting agents on cytoplasmic and nuclear non-protein sulphydryls: a fluorescence image cytometry study. Br J Cancer 72, 45-50.Thored, P., Arvidsson, A., Cacci, E., Ahlenius, H., Kallur, T., Darsalia, V., Ekdahl, C.T., Kokaia, Z., and Lindvall, O. (2006). Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells 24, 739-747.Tobin, M.K., Musaraca, K., Disouky, A., Shetti, A., Bheri, A., Honer, W.G., Kim, N., Dawe, R.J., Bennett, D.A., Arfanakis, K., et al. (2019). Human Hippocampal Neurogenesis Persists in Aged Adults and Alzheimer's Disease Patients. Cell Stem Cell 24, 974-982 e973.Torzewski, M., Waqar, A.B., and Fan, J. (2014). Animal models of C-reactive protein. Mediators Inflamm 2014, 683598.Tuo, Q.Z., Lei, P., Jackman, K.A., Li, X.L., Xiong, H., Li, X.L., Liuyang, Z.Y., Roisman, L., Zhang, S.T., Ayton, S., et al. (2017). Tau-mediated iron export prevents ferroptotic damage after ischemic stroke. Mol Psychiatry 22, 1520-1530.Tuo, Q.Z., Masaldan, S., Southon, A., Mawal, C., Ayton, S., Bush, A.I., Lei, P., and Belaidi, A.A. (2021). Characterization of Selenium Compounds for Anti-ferroptotic Activity in Neuronal Cells and After Cerebral Ischemia-Reperfusion Injury. Neurotherapeutics 18, 2682-2691.Ursini, F., Maiorino, M., Valente, M., Ferri, L., and Gregolin, C. (1982). Purification from Pig-Liver of a Protein Which Protects Liposomes and Biomembranes from Peroxidative Degradation and Exhibits Glutathione-Peroxidase Activity on Phosphatidylcholine Hydroperoxides. Biochim Biophys Acta 710, 197-211.van Praag, H., Kempermann, G., and Gage, F.H. (1999). Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2, 266-270.Vendeland, S.C., Deagen, J.T., Butler, J.A., and Whanger, P.D. (1994). Uptake of selenite, selenomethionine and selenate by brush border membrane vesicles isolated from rat small intestine. Biometals 7, 305-312.Vinceti, M., Michalke, B., Malagoli, C., Eichmuller, M., Filippini, T., Tondelli, M., Bargellini, A., Vinceti, G., Zamboni, G., and Chiari, A. (2019). Selenium and selenium species in the etiology of Alzheimer's dementia: The potential for bias of the case-control study design. J Trace Elem Med Biol 53, 154-162.Vukovic, J., Borlikova, G.G., Ruitenberg, M.J., Robinson, G.J., Sullivan, R.K., Walker, T.L., and Bartlett, P.F. (2013). Immature doublecortin-positive hippocampal neurons are important for learning but not for remembering. J Neurosci 33, 6603-6613.Wallenberg, M., Misra, S., Wasik, A.M., Marzano, C., Bjornstedt, M., Gandin, V., and Fernandes, A.P. (2014). Selenium induces a multi-targeted cell death process in addition to ROS formation. J Cell Mol Med 18, 671-684.Walter, J., Keiner, S., Witte, O.W., and Redecker, C. (2010). Differential stroke-induced proliferative response of distinct precursor cell subpopulations in the young and aged dentate gyrus. Neuroscience 169, 1279-1286.Wang, D., Liu, F., Zhu, L., Lin, P., Han, F., Wang, X., Tan, X., Lin, L., and Xiong, Y. (2020). FGF21 alleviates neuroinflammation following ischemic stroke by modulating the temporal and spatial dynamics of microglia/macrophages. J Neuroinflammation 17, 257.Wang, G., Wu, Y., Zhou, T., Guo, Y., Zheng, B., Wang, J., Bi, Y., Liu, F., Zhou, Z., Guo, X., et al. (2013). Mapping of the N-linked glycoproteome of human spermatozoa. J Proteome Res 12, 5750-5759.Wang, X., Mao, X., Xie, L., Sun, F., Greenberg, D.A., and Jin, K. (2012). Conditional depletion of neurogenesis inhibits long-term recovery after experimental stroke in mice. PLoS One 7, e38932.Wang, Z., Klipfell, E., Bennett, B.J., Koeth, R., Levison, B.S., Dugar, B., Feldstein, A.E., Britt, E.B., Fu, X., Chung, Y.M., et al. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57-63.Westendorp, W.F., Vermeij, J.D., Zock, E., Hooijenga, I.J., Kruyt, N.D., Bosboom, H.J., Kwa, V.I., Weisfelt, M., Remmers, M.J., ten Houten, R., et al. (2015). The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial. Lancet 385, 1519-1526.Wiesmann, M., Zinnhardt, B., Reinhardt, D., Eligehausen, S., Wachsmuth, L., Hermann, S., Dederen, P.J., Hellwich, M., Kuhlmann, M.T., Broersen, L.M., et al. (2017). A specific dietary intervention to restore brain structure and function after ischemic stroke. Theranostics 7, 493-512.Williamson, M.R. (2019). Stroke Primes New Hippocampal Neurons for Hyperexcitability. J Neurosci 39, 6396-6398.Williamson, M.R., Jones, T.A., and Drew, M.R. (2019). Functions of subventricular zone neural precursor cells in stroke recovery. Behav Brain Res 376, 112209.Willis, E.F., Bartlett, P.F., and Vukovic, J. (2017). Protocol for Short- and Longer-term Spatial Learning and Memory in Mice. Front Behav Neurosci 11, 197.Woitke, F., Ceanga, M., Rudolph, M., Niv, F., Witte, O.W., Redecker, C., Kunze, A., and Keiner, S. (2017). Adult hippocampal neurogenesis poststroke: More new granule cells but aberrant morphology and impaired spatial memory. PLoS One 12, e0183463.Wolf, A., Bauer, B., Abner, E.L., Ashkenazy-Frolinger, T., and Hartz, A.M. (2016). A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6/Tg2576 Mice. PLoS One 11, e0147733.Wu, A., Feng, B., Yu, J., Yan, L., Che, L., Zhuo, Y., Luo, Y., Yu, B., Wu, and Chen, D. (2021). Fibroblast growth factor 21 attenuates iron overload-induced liver injury and fibrosis by inhibiting ferroptosis. Redox Biol 46, 102131.Wu, S., Wu, B., Liu, M., Chen, Z., Wang, W., Anderson, C.S., Sandercock, P., Wang, Y., Huang, Y., Cui, L., et al. (2019). Stroke in China: advances and challenges in epidemiology, prevention, and management. Lancet Neurol 18, 394-405.Xiao, Y., Yuan, Y., Liu, Y., Yu, Y., Jia, N., Zhou, L., Wang, H., Huang, S., Zhang, Y., Yang, H., et al. (2019). Circulating Multiple Metals and Incident Stroke in Chinese Adults. Stroke 50, 1661-1668.Xiong, Z.G., Zhu, X.M., Chu, X.P., Minami, M., Hey, J., Wei, W.L., MacDonald, J.F., Wemmie, J.A., Price, M.P., Welsh, M.J., et al. (2004). Neuroprotection in ischemia: Blocking calcium-permeable acid-sensing ion channels. Cell 118, 687-698.Xu, J., Cheng, A., Song, B., Zhao, M., Xue, J., Wang, A., Dai, L., Jing, J., Meng, X., Li, H., et al. (2022). Trimethylamine N-Oxide and Stroke Recurrence Depends on Ischemic Stroke Subtypes. Stroke 53, 1207-1215.Xu, J., Wang, A., Meng, X., Yalkun, G., Xu, A., Gao, Z., Chen, H., Ji, Y., Xu, J., Geng, D., et al. (2021a). Edaravone Dexborneol Versus Edaravone Alone for the Treatment of Acute Ischemic Stroke: A Phase III, Randomized, Double-Blind, Comparative Trial. Stroke 52, 772-780.Xu, K., Gao, X., Xia, G., Chen, M., Zeng, N., Wang, S., You, C., Tian, X., Di, H., Tang, W., et al. (2021b). Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn. Gut.Xu, X.M., Turanov, A.A., Carlson, B.A., Yoo, M.H., Everley, R.A., Nandakumar, R., Sorokina, I., Gygi, S.P., Gladyshev, V.N., and Hatfield, D.L. (2010). Targeted insertion of cysteine by decoding UGA codons with mammalian selenocysteine machinery. Proc Natl Acad Sci U S A 107, 21430-21434.Yagita, Y., Kitagawa, K., Ohtsuki, T., Takasawa, K., Miyata, T., Okano, H., Hori, M., and Matsumoto, M. (2001). Neurogenesis by progenitor cells in the ischemic adult rat hippocampus. Stroke 32, 1890-1896.Yamaguchi, T., Sano, K., Takakura, K., Saito, I., Shinohara, Y., Asano, T., and Yasuhara, H. (1998). Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group. Stroke 29, 12-17.Yan, X., Liu, K., Sun, X., Qin, S., Wu, M., Qin, L., Wang, Y., Li, Z., Zhong, X., and Wei, X. (2020). A cross-sectional study of blood selenium concentration and cognitive function in elderly Americans: National Health and Nutrition Examination Survey 2011-2014. Ann Hum Biol, 1-26.Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K., and Masaki, T. (1988). A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332, 411-415.Yang, H., and Jia, X. (2014). Safety evaluation of Se-methylselenocysteine as nutritional selenium supplement: acute toxicity, genotoxicity and subchronic toxicity. Regul Toxicol Pharmacol 70, 720-727.Yang, H., Rajah, G., Guo, A., Wang, Y., and Wang, Q. (2018). Pathogenesis of epileptic seizures and epilepsy after stroke. Neurol Res 40, 426-432.Yang, J.G., Morrison-Plummer, J., and Burk, R.F. (1987). Purification and quantitation of a rat plasma selenoprotein distinct from glutathione peroxidase using monoclonal antibodies. J Biol Chem 262, 13372-13375.Yang, W.S., SriRamaratnam, R., Welsch, M.E., Shimada, K., Skouta, R., Viswanathan, V.S., Cheah, J.H., Clemons, P.A., Shamji, A.F., Clish, C.B., et al. (2014). Regulation of ferroptotic cancer cell death by GPX4. Cell 156, 317-331.Yang, Y., and Rosenberg, G.A. (2011). Blood–brain barrier breakdown in acute and chronic cerebrovascular disease. Stroke 42, 3323-3328.Yant, L.J., Ran, Q.T., Rao, L., Van Remmen, H., Shibatani, T., Belter, J.G., Motta, L., Richardson, A., and Prolla, T.A. (2003). The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radical Bio Med 34, 496-502.Yatsu, F.M., Lee, L.W., and Liao, C.L. (1975). Energy metabolism during brain ischemia. Stability during reversible and irreversible damage. Stroke 6, 678-683.Yeo, L.L., Paliwal, P., Teoh, H.L., Seet, R.C., Chan, B.P., Liang, S., Venketasubramanian, N., Rathakrishnan, R., Ahmad, A., Ng, K.W., et al. (2013). Timing of recanalization after intravenous thrombolysis and functional outcomes after acute ischemic stroke. JAMA Neurol 70, 353-358.Yousuf, S., Atif, F., Ahmad, M., Hoda, M.N., Khan, M.B., Ishrat, T., and Islam, F. (2007). Selenium plays a modulatory role against cerebral ischemia-induced neuronal damage in rat hippocampus. Brain Res 1147, 218-225.Zhang, R., Boareto, M., Engler, A., Louvi, A., Giachino, C., Iber, D., and Taylor, V. (2019). Id4 Downstream of Notch2 Maintains Neural Stem Cell Quiescence in the Adult Hippocampus. Cell Rep 28, 1485-1498.e1486.Zhang, R.L., Zhang, Z.G., Lu, M., Wang, Y., Yang, J.J., and Chopp, M. (2006). Reduction of the cell cycle length by decreasing G1 phase and cell cycle reentry expand neuronal progenitor cells in the subventricular zone of adult rat after stroke. J Cereb Blood Flow Metab 26, 857-863.Zhang, S., Rocourt, C., and Cheng, W.H. (2010). Selenoproteins and the aging brain. Mech Ageing Dev 131, 253-260.Zhang, X., Mei, Y., He, Y., Wang, D., Wang, J., Wei, X., Yang, E., Zhou, D., Shen, H., Peng, G., et al. (2021). Ablating Adult Neural Stem Cells Improves Synaptic and Cognitive Functions in Alzheimer Models. Stem Cell Reports 16, 89-105.Zhang, Y., Zhou, Y., Schweizer, U., Savaskan, N.E., Hua, D., Kipnis, J., Hatfield, D.L., and Gladyshev, V.N. (2008). Comparative analysis of selenocysteine machinery and selenoproteome gene expression in mouse brain identifies neurons as key functional sites of selenium in mammals. J Biol Chem 283, 2427-2438.Zhang, Z.H., Chen, C., Jia, S.Z., Cao, X.C., Liu, M., Tian, J., Hoffmann, P.R., Xu, H.X., Ni, J.Z., and Song, G.L. (2020). Selenium Restores Synaptic Deficits by Modulating NMDA Receptors and Selenoprotein K in an Alzheimer's Disease Model. Antioxid Redox Signal.Zhang, Z.H., Wu, Q.Y., Zheng, R., Chen, C., Chen, Y., Liu, Q., Hoffmann, P.R., Ni, J.Z., and Song, G.L. (2017). Selenomethionine Mitigates Cognitive Decline by Targeting Both Tau Hyperphosphorylation and Autophagic Clearance in an Alzheimer's Disease Mouse Model. Journal of Neuroscience 37, 2449-2462.Zheng, L., Xie, C., Zheng, J., Dong, Q., Si, T., Zhang, J., and Hou, S.T. (2021). An imbalanced ratio between PC(16:0/16:0) and LPC(16:0) revealed by lipidomics supports the role of the Lands cycle in ischemic brain injury. J Biol Chem 296, 100151.Zheng, R., Zhang, Z.H., Chen, C., Chen, Y., Jia, S.Z., Liu, Q., Ni, J.Z., and Song, G.L. (2017). Selenomethionine promoted hippocampal neurogenesis via the PI3K-Akt-GSK3beta-Wnt pathway in a mouse model of Alzheimer's disease. Biochem Biophys Res Commun 485, 6-15.Zhou, M., Wang, H., Zeng, X., Yin, P., Zhu, J., Chen, W., Li, X., Wang, L., Wang, L., Liu, Y., et al. (2019a). Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet.Zhou, Q.G., Nemes, A.D., Lee, D., Ro, E.J., Zhang, J., Nowacki, A.S., Dymecki, S.M., Najm, I.M., and Suh, H. (2019b). Chemogenetic silencing of hippocampal neurons suppresses epileptic neural circuits. J Clin Invest 129, 310-323.Zhu, W., Romano, K.A., Li, L., Buffa, J.A., Sangwan, N., Prakash, P., Tittle, A.N., Li, X.S., Fu, X., Androjna, C., et al. (2021a). Gut microbes impact stroke severity via the trimethylamine N-oxide pathway. Cell Host Microbe 29, 1199-1208 e1195.Zhu, X., Cabungcal, J.H., Cuenod, M., Uliana, D.L., Do, K.Q., and Grace, A.A. (2021b). Thalamic reticular nucleus impairments and abnormal prefrontal control of dopamine system in a developmental model of schizophrenia: prevention by N-acetylcysteine. Mol Psychiatry.Zille, M., Karuppagounder, S.S., Chen, Y., Gough, P.J., Bertin, J., Finger, J., Milner, T.A., Jonas, E.A., and Ratan, R.R. (2017). Neuronal Death After Hemorrhagic Stroke In Vitro and In Vivo Shares Features of Ferroptosis and Necroptosis. Stroke 48, 1033-1043.

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Zhuo Z. Potent Neuroprotective Effect of Selenium on Cerebral Ischemic Stroke[D]. 澳大利亚. 昆士兰大学,2022.
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