Enriched Environment Increases Neural Stem/Progenitor Cell Proliferation and Neurogenesis in the Subventricular Zone of Stroke-Lesioned Adult Rats

Abstract

Background and Purpose— The subventricular zone in the adult brain is identified as an endogenous resource of neuronal precursors that can be recruited to adjacent lesioned areas. The hypothesis was tested that postischemic environmental enrichment might enhance subventricular zone cell genesis. Methods— A cortical infarct was induced in adult spontaneously hypertensive rats by ligating the middle cerebral artery distal to the striatal branches, after which animals were housed in either standard or enriched environment and allowed to survive for 5 weeks. The thymidine analogue bromodeoxyuridine was administered during the first postischemic week. The generation of neural stem/progenitor cells and neuronal precursors in the subventricular zone were studied with cell specific markers such as Ki67 and phosphorylated histone H3 (cell proliferation), Sox-2 (neural stem/progenitor cells), bromodeoxyuridine (slowly cycling, nonmigratory putative neural stem cells), and doublecortin (newborn immature neurons). Results— Proliferating cells in the subventricular zone were identified as chiefly neural progenitors but also putative neural stem cells and neuronal precursors. Five weeks after stroke, proliferation in the subventricular zone was lower in stroke-lesioned rats housed in standard environment compared with nonlesioned rats. Postischemic environmental enrichment normalized cell proliferation levels, increased the numbers of putative neural stem cells as assessed with bromodeoxyuridine, and increased doublecortin-positive neuroblasts, which extended in migratory chains toward the infarct. Conclusions— Enriched environment increased the neural stem/progenitor cell pool and neurogenesis in the adult subventricular zone 5 weeks after a cortical stroke. This might be of potential importance for tissue regeneration.