TY  - JOUR
A1  - Kolbinger, Anja
A1  - Kestner, Roxane Isabelle
A1  - Jencio, Lara
A1  - Schäufele, Tim J.
A1  - Vutukuri, Rajkumar
A1  - Pfeilschifter, Waltraud
A1  - Scholich, Klaus
T1  - Behind the Wall - Compartment-Specific Neovascularisation during Post-Stroke Recovery in Mice
T2  - Cells
N2  - Ischemic stroke is a highly prevalent vascular disease leading to oxygen- and glucose deprivation in the brain. In response, ischemia-induced neovascularization occurs, which is supported by circulating CD34+ endothelial progenitor cells. Here, we used the transient middle cerebral artery occlusion (tMCAO) mouse model to characterize the spatio-temporal alterations within the ischemic core from the acute to the chronic phase using multiple-epitope-ligand cartography (MELC) for sequential immunohistochemistry. We found that around 14 days post-stroke, significant angiogenesis occurs in the ischemic core, as determined by the presence of CD31+/CD34+ double-positive endothelial cells. This neovascularization was accompanied by the recruitment of CD4+ T-cells and dendritic cells as well as IBA1+ and IBA1− microglia. Neighborhood analysis identified, besides pericytes only for T-cells and dendritic cells, a statistically significant distribution as direct neighbors of CD31+/CD34+ endothelial cells, suggesting a role for these cells in aiding angiogenesis. This process was distinct from neovascularization of the peri-infarct area as it was separated by a broad astroglial scar. At day 28 post-stroke, the scar had emerged towards the cortical periphery, which seems to give rise to a neuronal regeneration within the peri-infarct area. Meanwhile, the ischemic core has condensed to a highly vascularized subpial region adjacent to the leptomeningeal compartment. In conclusion, in the course of chronic post-stroke regeneration, the astroglial scar serves as a seal between two immunologically active compartments—the peri-infarct area and the ischemic core—which exhibit distinct processes of neovascularization as a central feature of post-stroke tissue remodeling. Based on our findings, we propose that neovascularization of the ischemic core comprises arteriogenesis as well as angiogenesis originating from the leptomenigeal vasculature.
KW  - stroke
KW  - angiogenesis
KW  - dendritic cell
KW  - microglia
KW  - T-cell
KW  - multiplex immunohistochemistry
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/81846
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-818465
SN  - 2073-4409
N1  - This work was supported by the DFG grants SFB1039 (TP A08 and B08) SCHO817/3-3, GRK2336 (TP07), Cardio-Pulmonary Institute (CPI), EXC 2026, Project ID: 390649896 and the LOEWE initiative ACLF-I and the Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD), Frankfurt/Main, Germany.
VL  - 11
IS  - 10, art. 1659
SP  - 1
EP  - 15
PB  - MDPI
CY  - Basel
ER  -