Continued dysfunction of capillary pericytes promotes no-reflow after experimental stroke in vivo.

Autor:	Shrouder JJ; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany., Calandra GM; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany., Filser S; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.; Core Research Facilities and Services-Light Microscope Facility, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany., Varga DP; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany., Besson-Girard S; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany., Mamrak U; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany., Dorok M; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany., Bulut-Impraim B; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany., Seker FB; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany., Gesierich B; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany., Laredo F; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany., Wehn AC; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.; Department of Neurosurgery, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany., Khalin I; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.; Normandie University, UNICAEN, INSERM UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), GIP Cyceron, Institute Blood and Brain @ Caen-Normandie (BB@C), 14000 Caen, France., Bayer P; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany., Liesz A; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany., Gokce O; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany., Plesnila N; Institute for Stroke and Dementia Research (ISD), LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, 81377 Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2024 Mar 01; Vol. 147 (3), pp. 1057-1074.
DOI:	10.1093/brain/awad401
Abstrakt:	Incomplete reperfusion of the microvasculature ('no-reflow') after ischaemic stroke damages salvageable brain tissue. Previous ex vivo studies suggest pericytes are vulnerable to ischaemia and may exacerbate no-reflow, but the viability of pericytes and their association with no-reflow remains under-explored in vivo. Using longitudinal in vivo two-photon single-cell imaging over 7 days, we showed that 87% of pericytes constrict during cerebral ischaemia and remain constricted post reperfusion, and 50% of the pericyte population are acutely damaged. Moreover, we revealed ischaemic pericytes to be fundamentally implicated in capillary no-reflow by limiting and arresting blood flow within the first 24 h post stroke. Despite sustaining acute membrane damage, we observed that over half of all cortical pericytes survived ischaemia and responded to vasoactive stimuli, upregulated unique transcriptomic profiles and replicated. Finally, we demonstrated the delayed recovery of capillary diameter by ischaemic pericytes after reperfusion predicted vessel reconstriction in the subacute phase of stroke. Cumulatively, these findings demonstrate that surviving cortical pericytes remain both viable and promising therapeutic targets to counteract no-reflow after ischaemic stroke. (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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