Effects of Specific Sensorimotor Forelimb Training on Endogenous Stem Cell Proliferation and Differentiation in the Dentate Gyrus after Focal Brain Ischemia

Neurogenesis is known to occur throughout life in the dentate gyrus of rodents and is modulated by different specific but also unspecific stimuli (e.g., enriched environment). In this study we investigated the effects of specific sensorimotor training on neurogenesis in the dentate gyrus of adult rats after focal brain ischemia. Small cortical photothrombotic infarcts (PT) were induced in the forelimb sensorimotor cortex. We compared one group of animals receiving daily reaching training (RT) of the impaired forelimb with a standard housing group (ST). Every group consisted of lesioned animals (PT) and sham-operated animals (Sham), respectively. We examined cell proliferation and differentiation at two different time points, 10 days and 42 days post surgery. All animals obtained daily injections of the proliferation marker bromodeoxyuridine (BrdU, 50mg/kg) five times, from day 2 until day 6 post surgery. After 10 days ST-PT as well as RT-PT animals showed a significant increase in total number of BrdU-labeled cells compared with sham-operated controls (ST-Sham, RT-Sham), but there was no difference between trained (RT) and standard housed (ST) animals. At 42 days after the infarct, the RT-PT group revealed about 30% more newborn cells than standard housed animals with cortical infarcts (ST-PT group). However, this training-induced increase was much higher (approx. 100–120%) in the RT-Sham group compared with the ST-Sham group. The neuronal and glial differentiation of these cells was analyzed using confocal microscopy. The present study clearly demonstrates that specific sensorimotor forelimb training significantly increases the survival of new-born progenitor cells in the dentate gyrus after cortical infarcts. Remarkably, these training-induced effects on cell survival are considerably higher in animals without cortical infarcts. Supported by DFG Re1315/3–1 and IZKF Jena.