Fetal Kidney Tissue Transplantation And Bmp-7-induced Ne

National Institute On Drug Abuse

Investigators

Linked publications & trials

Abstract

Both bone morphogenetic protein-7 (BMP-7) and glial cell line derived neurotrophic factor (GDNF) reduce ischemia-induced cerebral injury in rats. Intracerebral transplantation of fetal kidney tissue, in which BMP-7 and GDNF play important roles during development, reduced ischemic injury in cerebral cortex. In this study, we tested the hypothesis that BMP-7 is involved in this neuroprotective response. Fetal kidney tissues were cut into small pieces and transplanted into cortical areas adjacent to the right middle cerebral artery (MCA) distribution in anesthetized adult Sprague-Dawley rats. In situ hybridization study indicates that these fetal kidney transplants contained high levels of BMP-7 mRNA 3 days after grafting. Some animals were grafted with fetal kidney tissues after intraventricular administration (ICV) of the BMP-7 antagonist noggin (1 mg) or after ICV vehicle. The right MCA was later transiently ligated for 60 min. Animals receiving fetal kidney tissue transplantation developed significantly less body asymmetry, as compared to stroke animals that received no transplantation, or that received fetal kidney grafts and noggin pretreatment. Animals were later sacrificed and brains were removed for triphenyltetrazolium chloride staining. We found that transplantation of fetal kidney tissue reduced the volume of infarction in the cerebral cortex. Noggin pretreatment reduced the protection induced by fetal kidney grafting. A subgroup of animals were sacrificed 8 hours after ischemia for assay of caspase-3 enzymatic activity. Fetal kidney grafts significantly reduced ischemia-induced caspase-3 activity. This reduction could also be antagonized by noggin. In conclusion, our data suggest that fetal kidney transplantation reduces ischemia/reperfusion -induced cortical infarction and behavioral deficits in adult rats, which are, at least partially, mediated through the effect of BMP-7 in the transplants.