We have previously reported that intracerebral administration of glial cell line derived neurotrophic factor (GDNF) reduces middle cerebral artery (MCA)-ligation-induced cortical infarction in rats. Recent studies have indicated that application of 1,25 dihydroxyvitamin D3(D3) enhances GDNF mRNA expression in vitro. If D3 can increase GDNF expression in the brain, it is possible that administration of D3 can protect against ischemic brain injury. We found that pretreatment with D3 for 7 day showed a significant reduction in motor impairment and area of infarction in the cortex after MCA ligation. We also found that pre-treatment with D3 facilitates the expression of GDNF receptor alpha (GFRalpha-1) in cortex. Taken together, our data suggest that D3 reduces ischemia-induced brain damage possibly through the upregulation of GDNF receptors in cortex. This work will be presented at the Neuroscience Meeting, 1998. It has also been reported that fetal but not adult kidney tissues contain high concentration of trophic factors such as GDNF and neurturin. It is possible that transplantation of fetal kidney tissue can protect against injury in the ischemic brain by providing these trophic factors. We found that grafting of fetal kidney tissue, obtained at gestational day of 16, elicited a significant reduction in MCA ligation-induced infarction. On the other hand, transplantation of adult kidney tissue or injection of saline did not reduce the volume of infarction in cerebral cortex. Taken together, our data indicate that fetal kidney transplantation reduces ischemia-induced injury in the cerebral cortex, possibly through supplying of trophic factors to the ischemic brain. The findings will be presented at the Neuroscience Meeting 1998.