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Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke11.56 MB
Published VersionCC BY-NC V4.0, Open Access
Journal article
Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke
Journal of the American Heart Association, Vol.12(11), pp.1-25
2023
PMID: 37232244
Abstract
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.
Details
- Title
- Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke
- Authors
- Christian Staehr (Corresponding Author) - Aarhus UniversityJohn T Giblin (Author) - Boston UniversityEugenio Gutiérrez-Jiménez (Author) - Aarhus UniversityHalvor Ø Guldbrandsen (Author) - Aarhus UniversityJianbo Tang (Author) - Boston UniversityShaun L Sandow (Author) - University of the Sunshine Coast, Queensland, School of Health - BiomedicineDavid A Boas (Author) - Boston UniversityVladimir V Matchkov (Author) - Aarhus University
- Publication details
- Journal of the American Heart Association, Vol.12(11), pp.1-25
- Publisher
- Wiley-Blackwell Publishing, Inc.
- Date published
- 2023
- DOI
- 10.1161/JAHA.123.029527
- ISSN
- 2047-9980
- PMID
- 37232244
- Copyright note
- © 2023 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
- Grant note
- nr.: 8073-00007B/ The International Network Programme 8020-00084B/ The Independent Research Fund Denmark–Medical Sciences R344-2020-952/ Lundbeck Foundation #2021-35/ Helga & Peter Korning’s Foundation
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland
- Language
- English
- Record Identifier
- 99731498302621
- Output Type
- Journal article
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