Behind the Wall-Compartment-Specific Neovascularisation during Post-Stroke Recovery in Mice

• Published in: Cells (Basel, Switzerland) Switzerland), 2022-05, Vol.11 (10), p.1659
• Main Authors: Kolbinger, Anja, Kestner, Roxane Isabelle, Jencio, Lara, Schäufele, Tim J, Vutukuri, Rajkumar, Pfeilschifter, Waltraud, Scholich, Klaus
• Format: Article
• Language: English
• Subjects: Angiogenesis; Antibodies; Automation; Brain research; CD34 antigen; CD4 antigen; Cerebral blood flow; dendritic cell; Dendritic cells; Endothelial cells; Endothelium; Epitopes; Immunohistochemistry; Ischemia; Laboratory animals; Lymphocytes T; Meninges; Microglia; multiplex immunohistochemistry; Neural stem cells; Pericytes; Progenitor cells; Regeneration; Statistical analysis; Stroke; T-cell; Vascular diseases; Vascularization; Veins & arteries
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells11101659

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.