A Novel Population of α-Smooth Muscle Actin-Positive Cells Activated in a Rat Model of Stroke: An Analysis of the Spatio-Temporal Distribution in Response to Ischemia

Abstract

In a rat model of stroke, the spatio-temporal distribution of α-smooth muscle actin-positive, (αSMA+) cells was investigated in the infarcted hemisphere (ipsilateral) and compared with the contralateral hemisphere. At day 3 postischemia, αSMA+ cells were concentrated in two main loci within the ipsilateral hemisphere (Area A) in the medial corpus callosum and (Area B) midway through the striatum adjacent to the lateral ventricle. By day 7 and further by day 14, fewer αSMA+ cells remained in Areas A and B but a steady increase in the peri-infarct was observed. αSMA+ cells also expressed glial acidic fibrillary protein [GFAP: αSMA+/GFAP+ (29%); αSMA+/GFAP- (71%) phenotypes] and feline leukemia virus C receptor 2 (FLVCR2), but not ED1(microglia) and established markers of pericytes normally located in vascular wall. αSMA+ cells were also located close to the subventricular zones (SVZ) adjacent to Areas A and B. In conclusion, αSMA+ cells have been identified in a spatial and temporal sequence from the SVZ, at intermediate loci and in the vicinity of the peri-infarct. It is hypothesized that novel populations of αSMA+ precursors of pericytes are born on the SVZ, migrate into the peri-infarct region and are incorporated into new vessels of the peri-infarct regions.

Single-Cell Transcriptomics and Fate Mapping of Ependymal Cells Reveals an Absence of Neural Stem Cell Function

“…Importantly, cells marked by aSMA::R26 in the V-SVZ did not exhibit astrocytic morphology, showing only rare co-expression of GFAP (GFAP +ve : 5/159 cells, n = 6 mice, Figure 1J) yet were closely associated with GFAP +ve sub-ependymal cells and were non-proliferative, as evidenced by an absence of Ki67 staining (Ki67 +ve : 0/47 cells, n = 3 mice; Figure 1K). As expected of the aSMA promoter, other recombined cells identified throughout the brain were from mural cells, including smooth muscle cells associated with CD31 +ve blood vessels and a previously described rare population of integrin a9 +ve densely fibrous putative pericyte-precursors (Figures S1A and S1B;Sharma et al, 2012). Critically, after 2-5 months of fate mapping, we found no evidence of recombined cell contribution to olfactory bulb neurogenesis (0 cells, n = 5 mice, Figure 1N).…”

Microvesicles from brain-extract—treated mesenchymal stem cells improve neurological functions in a rat model of ischemic stroke

“…Sharma et al . 45 reported that the number of α-SMA-positive cells increased in the infarct region up to day 7, and thereafter incorporated into small vessels in a rat pMCAO-induced stroke model. In agreement with recent studies, our results suggest that MSC-MVs treated with brain extract have therapeutic effects on vascular remodelling (angiogenesis and arteriogenesis) after ischemic stroke.…”

Endogenous Brain Pericytes Are Widely Activated and Contribute to Mouse Glioma Microvasculature

“…The SVZ is an active proliferative zone within the brain and this region has previously been shown to be reactive and produce nestin and doublecortin positive neuroblasts in response to glioma [ 32 , 33 ]. Furthermore, in response to local cerebral ischemia, precursors of pericytes within the SVZ proliferate and migrate to the infarcted area where they are incorporated into new vessels of the peri-infarct regions [ 34 ]. Whether pericyte activation in the SVZ facilitates this process remains to be established.…”