Effects of skilled forelimb training on hippocampal neurogenesis and spatial learning after focal cortical infarcts in the adult rat brain.

BACKGROUND AND PURPOSE Environmental stimulation consistently increases dentate neurogenesis in the adult brain and improves spatial learning. We tested the hypothesis whether specific rehabilitative training of an impaired forelimb influences these processes after focal cortical infarcts. METHODS Focal cortical infarcts were induced in the forelimb sensorimotor cortex using the photothrombosis model. One group of infarcted animals and sham-operated controls housed in standard cages received one daily session of skilled reaching training of the impaired or dominant forelimb, respectively. A second group was transferred to an enriched environment, whereas a third group remained in the standard cages without further treatment. Bromodeoxyuridine was administered from day 2 until day 6 postinfarct. Proliferation and differentiation of newborn cells was analyzed at day 10 and 42 using immunocytochemistry with neuronal and glial markers and confocal laser scanning microscopy. Spatial learning was tested in the Morris water maze between days 35 and 41. RESULTS After cortical infarcts in the forelimb sensorimotor cortex, environmental enrichment as well as daily reaching training of the impaired paw both increase dentate neurogenesis and improve functional performance in the Morris water maze. Nevertheless, the reaching training-induced neurogenic response was significantly greater in nonlesioned controls associated with the best spatial learning performance in the water maze. CONCLUSIONS Skilled forelimb training effectively stimulates dentate neurogenesis and spatial learning in the infarcted and healthy brain. However, this reaching training-induced increase in neurogenesis was reduced after cortical infarcts.