Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice

Zhuo，Zhan1,2; Wang，Huimei1,3; Zhang，Shuai1; Bartlett，Perry F.2; Walker，Tara L.2; Hou，Sheng Tao1

2023-07-01

10.1177/0271678X231156981

Journal of Cerebral Blood Flow and Metabolism   Impact Factor & Quartile

0271-678X

1559-7016

Despite progress in reperfusion therapy, functional recovery remains suboptimal in many stroke patients, with oxidative stress, inflammation, dysbiosis, and secondary neurodegeneration constituting the major hurdles to recovery. The essential trace element selenium is emerging as a promising therapeutic agent for stroke. However, although several rodent studies have shown that selenium can protect against cell loss following cerebral ischemia, no study has yet examined whether selenium can enhance long-term functional recovery. Moreover, published studies have typically reported a single mechanism of action underlying selenium-mediated stroke recovery. However, we propose that selenium is more likely to have multifaceted actions. Here, we show that selenomethionine confers a potent neuroprotective effect in a canonical filament-induced transient middle cerebral artery occlusion (tMCAO) mouse model. Post-tMCAO selenium treatment significantly reduces the cerebral infarct volume, oxidative stress, and ferroptosis and enhances post-tMCAO motor performance in the acute phase after stroke. Moreover, analysis of the gut microbiota reveals that acute selenium treatment reverses stroke-induced gut dysbiosis. Longer-term selenium supplementation activates intrinsic neuroprotective mechanisms, prevents secondary neurodegeneration, alleviates systemic inflammation, and diminishes gut microbe-derived circulating trimethylamine N-oxide. These findings demonstrate that selenium treatment even after cerebral ischemia has long-term and multifaceted neuroprotective effects, highlighting its clinical potential.

ischemia/reperfusion injury neuroprotection oxidative stress selenium Stroke trimethylamine N-oxide

SCI

English

First ; Corresponding

National Natural Science Foundation of China[81871026] ; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions["2021SHIBS0002","2022HIBS0002"] ; Shenzhen Science and Technology Innovation Committee[JCYJ20180504165806229]

Endocrinology & Metabolism ; Hematology ; Neurosciences & Neurology

Endocrinology & Metabolism ; Hematology ; Neurosciences

WOS:000930726000001

SAGE PUBLICATIONS INC

NEUROSCIENCE & BEHAVIOR

2-s2.0-85147758553

Scopus

1.Brain Research Centre,Department of Biology,School of Life Science,Southern University of Science and Technology,Shenzhen,China
2.Queensland Brain Institute,The University of Queensland,Brisbane,Australia
3.Hearing Research Group,Department of Anatomy and Neurobiology,College of Medicine,Northeast Ohio Medical University,Rootstown,United States

Zhuo，Zhan,Wang，Huimei,Zhang，Shuai,et al. Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice[J]. Journal of Cerebral Blood Flow and Metabolism,2023,43(7):1060-1076.

Zhuo，Zhan,Wang，Huimei,Zhang，Shuai,Bartlett，Perry F.,Walker，Tara L.,&Hou，Sheng Tao.(2023).Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice.Journal of Cerebral Blood Flow and Metabolism,43(7),1060-1076.

Zhuo，Zhan,et al."Selenium supplementation provides potent neuroprotection following cerebral ischemia in mice".Journal of Cerebral Blood Flow and Metabolism 43.7(2023):1060-1076.