Enriched Environment Attenuates Cell Genesis in Subventricular Zone After Focal Ischemia in Mice and Decreases Migration of Newborn Cells to the Striatum

Abstract

Background and Purpose— Cells proliferate continuously in the adult mammalian brain, and in rodents, cell genesis is affected by housing conditions and brain injury. Increase in neurogenesis after brain ischemia has been postulated to be linked to functional recovery after stroke. Housing rodents in an enriched environment improves motor function after stroke injury. We have investigated whether changes in cell genesis can explain the beneficial effects of an enriched environment. Methods— Intact mice and mice subjected to transient occlusion of the middle cerebral artery were exposed to an enriched environment for 1 month. Bromodeoxyuridine was injected daily to label proliferating cells during the first postischemic week. Newborn cells were analyzed immunohistochemically after 4 weeks. Results— The enriched environment increased neurogenesis in the dentate gyrus in both intact and stroke-injured animals. An increased number of newborn cells was found in the subventricular zone of stroke-injured mice, but not in injured mice exposed to an enriched environment. Also, the number of newborn astrocytes (BrdU+/S-100β+ cells), neuroblasts (dcx+ cells), and reactive astrocytes (vimentin mRNA) in the striatum ipsilateral to the ischemic injury was markedly attenuated and new adult neurons (BrdU+/NeuN+) were not found. The enriched environment did not affect infarct size or mortality. Conclusions— An enriched environment after experimental stroke increased neurogenesis in the hippocampus, whereas there was a decreased cell genesis and migration of neuroblasts and newborn astrocytes in the striatum.