Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke

Staehr，Christian1,2; Giblin，John T.2; Gutiérrez-Jiménez，Eugenio3; Guldbrandsen，Halvor1; Tang，Jianbo2,4; Sandow，Shaun L.5,6; Boas，David A.2; Matchkov，Vladimir V.1

2023-06-06

10.1161/JAHA.123.029527

Journal of the American Heart Association   Impact Factor & Quartile

2047-9980

BACKGROUND: Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular coupling, such as the local hyperemic response to neuronal activity, may contribute to poor neurological outcome after stroke despite successful recanalization, that is, futile recanalization. METHODS AND RESULTS: Mice implanted with chronic cranial windows were trained for awake head-fixation before experiments. One-hour occlusion of the anterior middle cerebral artery branch was induced using single-vessel photothrombosis. Cerebral perfusion and neurovascular coupling were assessed by optical coherence tomography and laser speckle contrast imaging. Capillaries and pericytes were studied in perfusion-fixed tissue by labeling lectin and platelet-derived growth factor receptor β. Arterial occlusion induced multiple spreading depolarizations over 1 hour associated with substantially reduced blood flow in the peri-ischemic cortex. Approximately half of the capillaries in the peri-ischemic area were no longer perfused at the 3-and 24-hour follow-up (45% [95% CI, 33%– 58%] and 53% [95% CI, 39%– 66%] reduction, respectively; P<0.0001), which was associated with contraction of an equivalent proportion of peri-ischemic capillary pericytes. The capillaries in the peri-ischemic cortex that remained perfused showed increased point prevalence of dynamic flow stalling (0.5% [95% CI, 0.2%– 0.7%] at baseline, 5.1% [95% CI, 3.2%– 6.5%] and 3.2% [95% CI, 1.1%– 5.3%] at 3-and 24-hour follow-up, respectively; P=0.001). Whisker stimulation at the 3-and 24-hour follow-up led to reduced neurovascular coupling responses in the sensory cortex corresponding to the peri-ischemic region compared with that observed at baseline. CONCLUSIONS: Arterial occlusion led to contraction of capillary pericytes and capillary flow stalling in the peri-ischemic cortex. Capillary dysfunction was associated with neurovascular uncoupling. Neurovascular coupling impairment associated with capillary dysfunction may be a mechanism that contributes to futile recanalization. Hence, the results from this study suggest a novel treatment target to improve neurological outcome after stroke.

capillaries ischemic stroke neurovascular coupling penumbra pericytes

SCI

English

Others

Danish Agency for Science and Higher Education[8073-00007B];

Cardiovascular System & Cardiology

Cardiac & Cardiovascular Systems

WOS:001001920100018

WILEY

2-s2.0-85162040788

Scopus

1.Department of Biomedicine,Aarhus University,Aarhus,Denmark
2.Neurophotonics Center,Department of Biomedical Engineering,Boston University,Boston,United States
3.Center of Functionally Integrative Neuroscience,Institute for Clinical Medicine,Aarhus University,Aarhus,Denmark
4.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,China
5.Biomedical Science,School of Health,University of the Sunshine Coast,Sippy Downs,Australia
6.Centre for Clinical Research,Faculty of Medicine,The University of Queensland,Brisbane,Australia

Staehr，Christian,Giblin，John T.,Gutiérrez-Jiménez，Eugenio,et al. Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke[J]. Journal of the American Heart Association,2023,12(11).

Staehr，Christian.,Giblin，John T..,Gutiérrez-Jiménez，Eugenio.,Guldbrandsen，Halvor.,Tang，Jianbo.,...&Matchkov，Vladimir V..(2023).Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke.Journal of the American Heart Association,12(11).

Staehr，Christian,et al."Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke".Journal of the American Heart Association 12.11(2023).