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

Shrouder, Joshua James; Calandra, Gian Marco; Filser, Severin; Varga, Daniel Peter; Besson-Girard, Simon; Mamrak, Uta; Dorok, Maximilian; Bulut-Impraim, Buket; Seker, Fatma Burcu; Gesierich, Benno; Laredo, Fabio; Wehn, Antonia Clarissa; Khalin, Igor; Bayer, Patrick; Liesz, Arthur; Gokce, Ozgun und Plesnila, Nikolaus (2024): Continued dysfunction of capillary pericytes promotes no-reflow after experimental stroke in vivo. In: Brain, Bd. 147, Nr. 3: S. 1057-1074

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 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. Incomplete reperfusion of the microvasculature ('no-reflow') after ischaemic stroke damages salvageable brain tissue. Shrouder et al. show that pericytes constrict capillaries after experimental ischaemic stroke and contribute to no-reflow. Despite sustaining damage, surviving pericytes remain viable and could be promising therapeutic targets.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198