Improvement of focal ischemia-induced rat dopaminergic dysfunction by striatal transplantation of mouse embryonic stem cells

Middle cerebral artery occlusion (MCAO) caused behavioral dysfunction with massive neuronal loss. Cell transplantation may recover this deficit by replacing damaged brain cells. In this study, we examined the effects of transplantation of mouse embryonic stem (ES) cells or ES cell-derived neuron-like (ES-N) cells on behavioral function in ischemic rats. Seven days after MCAO, ES or ES-N cells were transplanted into ipsilateral striata (but not the substantia nigra) of ischemic rats. Transplanted rats exhibited a gradual reduction in the number of rotations induced by methamphetamine compared to vehicle-injected rats. These rats also showed a significant improvement in rota-rod performance. At 15 weeks after transplantation, immunoreactivities for tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the striatum were significantly recovered in rats grafted with ES or ES-N cells compared to vehicle-injected rats. These results suggest that intrastriatal-transplantation of ES or ES-N cells improved the dopaminergic function and subsequently recover behavioral dysfunction in focal ischemic rats.