Regeneration of neuronal function by grafting neural stem cells

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To determine the possible therapeutic potential of neural stem cells (NSCs) introduced into the damaged central nervous system, we examined a synapse formation and an integration of adult hippocampus-derived NSCs.First, we demonstrated that adult NSCs can differentiate into neurons with functional glutamatergic and GABAergic synaptic transmission in vitro. These results support the concept that such neurons could integrate into the neuronal circuitry (Exp. Neurol. 165 : 66-76, 2000).Next, we grafted these NSCs into the hippocampus of rats with transient global ischemia. Transient four-vessel occlusion yielded 90 to 95 % losses of pyramidal neurons in the hippocampal CA1 region. In this region, 1 to 3 % of the grafted cells survived ; and 3 to 9 % of them expressed NeuN, a neuronal marker. Rats with more than 120 NeuN-positive cells showed partial improvement of impaired spatial learning in a water maze test. These results suggest that NSCs grafted in the ischemic brain are able to differentiate into neurons and to improve spatial recognition (Neurosci. Lett. 316 : 9-12, 2001).As another model of neuronal damage, epileptic rats are under construction. We have produced rats with cortical dysplasia by exposing rat fetus in the uterus to UV light. These rats will also be subjected to transplantation of NSCs.