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

• DOI: 10.1093/brain/awad401
• Publication Date: 2023-12-28T14:19:51Z
• Authors: Joshua James Shro...; Gian Marco Calandra; Severin Filser; Daniel Peter Varga; Simon Besson-Girard; Uta Mamrak; Maximilian Dorok; Buket Bulut-Impraim; Fatma Burcu Seker; Benno Gesierich; Fabio Laredo; Antonia Clarissa ...; Igor Khalin; Patrick Bayer; Arthur Liesz; Ozgun Gokce; Nikolaus Plesnila
• Keywords: Pericyte; Stroke; Ex vivo; Brain ischemia

Abstract 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 viability their association with no-reflow remains under-explored in vivo. Using longitudinal two-photon single-cell imaging over 7 days, we showed that 87% constrict during cerebral remain constricted post reperfusion, 50% pericyte population acutely damaged. Moreover, revealed be fundamentally implicated capillary by limiting arresting blood flow within first 24 h stroke. Despite sustaining acute membrane damage, observed half all cortical survived responded vasoactive stimuli, upregulated unique transcriptomic profiles replicated. Finally, demonstrated delayed recovery diameter predicted vessel reconstriction subacute phase Cumulatively, these findings demonstrate surviving both viable promising therapeutic targets counteract