Effects of sensorimotor forelimb training and environmental enrichment on neurogenesis in the dentate gyrus after focal cortical infarcts

Neurogenesis is known to occur throughout life in the dentate gyrus of rodents and is modulated by learning, physical activity and environmental enrichment. Only little is known about these activity-dependent changes in neurogenesis after brain insults such as stroke. In this study we investigated the effects of specific sensorimotor training and unspecific activation in an enriched environment on neurogenesis in the dentate gyrus of adult rats after focal brain ischemia. In this study we induced cortical infarcts in the forelimb cortex and analyzed the effects of daily reaching training of the impaired forelimb, housing in an environmental enrichment, and standard housing conditions on progenitor cell proliferation and differentiation in the dentate gyrus. At 10 and 42 days after the infarct the animals were sacrificed and processed for immunhistochemistry with antibodies against the proliferation marker bromodesoxyuridine as well as mature neuronal (NeuN) and glial (S100beta) markers. We demonstrate that specific sensorimotor training of the impaired forelimb but also unspecific environmental enrichment significantly increase neurogenesis in the dentate gyrus after cortical infarcts associated with a better behavioral performance in the Morris water maze. However, the effects of reaching training were even stronger in unlesioned control animals, indicating that cortical infarcts at least in part inhibit training-induced neurogenesis in the dentate gyrus. These findings might contribute to a better understanding of the cellular plasticity of endogenous progenitor cells after focal stroke and the effects of rehabilitative interventions.

Supported by DFG Re1315/3–1 and IZKF Jena