Effects of Environmental Enrichment on Endogenous Stem Cell Proliferation and Differentiation in the Dentate Gyrus after Focal Brain Ischemia

Activity significantly influences endogeneous stem cell proliferation and neurogenesis under physiological conditions, but only little is known about the effects of environmental stimulation on these processes following brain insults like focal ischemic stroke. In the present study, we analyzed the proliferative response and differentiation of progenitor cells in the dentate gyrus after focal cortical infarcts in adult rats. Photothrombotic infarcts (PT) were induced in the forelimb sensorimotor cortex and the proliferation marker bromodeoxyuridine (BrdU, 50mg/kg per day) was injected intraperitoneally at day 3 to day 7 after the surgery. Controls received a sham surgery. The animals were either housed in standard conditions (ST-Sham, ST-PT) or in an enriched environment (EE-Sham, EE-PT) for 10 or 42 days. BrdU incorporation and differentiation were immunocytochemically analyzed using light and confocal microscopy. After 10 days the number of BrdU-labelled cells was significantly increased in ST-PT animals compared to ST-Sham controls. EE housing did not enhance the number of BrdU-positive cells in EE-PT animals compared with the ST-PT group and only a slight increase was observed in EE-Sham compared with ST-Sham. However, 42 days after ischemia animals held in the enriched environment (EE-PT) showed a significant postischemic increase in total number of BrdU-labelled cells compared with standard conditions (PT-ST). The present study clearly demonstrates that environmental enrichment after focal stroke increases the survival of newborn cells in the dentate gyrus. Supported by DFG Re 1315/3–1.