Transplantation of fetal kidney tissue reduces cerebral infarction inducedby middle cerebral artery ligation

The authors, and others, have recently reported that intracerebral administ ration of glial cell line-derived neurotrophic factor (GDNF) or osteogenic protein-1 protects against ischemia-induced injury in the cerebral cortex o f adult rats. Because these trophic factors are highly expressed in the fet al, but not adult, kidney cortex, the possibility that transplantation of f etal kidney tissue could serve as a cellular reservoir for such molecules a nd protect against ischemic injury in cerebral cortex was examined. Fetal k idneys obtained from rat embryos at gestational day 16, and adult kidney co rtex, were dissected and cut into small pieces. Adult male Sprague-Dawley r ats were anesthetized with chloral hydrate and placed in a stereotactic app aratus. Kidney tissues were transplanted into three cortical areas adjacent to the right middle cerebral artery (MCA). Thirty minutes after grafting, the right MCA was transiently ligated for 90 minutes. Twenty-four hours aft er the onset of reperfusion, animals were evaluated behaviorally. It was fo und that the stroke animals that received adult kidney transplantation deve loped motor imbalance. However, animals that received fetal kidney grafts s howed significant behavioral improvement. Animals were later sacrificed and brains were removed for triphenyltetrazolium chloride staining, Pax-2 immu nostaining, and GDNF mRNA expression. It was noted that transplantation of fetal kidney but not adult kidney tissue greatly reduced the volume of infa rction in the cerebral cortex. Fetal kidney grafts showed Pax-2 immunoreact ivity and GDNF mRNA in the host cerebral cortex. In contrast, GDNF mRNA exp ression was not found in the adult kidney grafts. Taken together, our data indicate that fetal kidney transplantation reduces ischemia/reperfusion-ind uced cortical infarction and behavioral deficits in adult rats, and that su ch tissue grafts could serve as an unique cellular reservoir for trophic fa ctor application to the brain.