Protective effects of glial cell line-derived neurotrophic factor on hippocampal neurons after traumatic brain injury in rats

Object. The purpose of this study was to evaluate whether glial cell line-d erived neurotrophic factor (GDNF) can protect against hippocampal neuronal death after traumatic brain injury (TBI). Methods. Male Sprague-Dawley rats were subjected to moderate TBI with a con trolled cortical impact device while in a state of halothane-induced anesth esia. Then, GDNF or artificial cerebrospinal fluid ([aCSF]; vehicle) was in fused into the frontal horn of the left lateral ventricle. In eight brain-i njured and eight sham-operated rats, GDNF was infused continuously for 7 da ys (200 ng/day intracerebroventricularly at a rate of 8.35 ng/0.5 mul/hour) . An equal volume of vehicle was infused at the same rate into the remainin g eight brain-injured and eight sham-operated rats. Seven days postinjury, all rats were killed. Their brains were sectioned and stained with cresyl v iolet, and the hippocampal neuronal loss was evaluated in the CA2 and CA3 r egions with the aid of microscopy. A parallel set of sections from each bra in was subjected to immunoreaction with antibodies against glial fibrillary acidic protein (GFAP; astroglia marker). In the aCSF-treated group, TBI re sulted in a significant neuronal loss in the CA2 (60%, p < 0.05) and CA3 re gions (68%, p < 0.05) compared with the sham-operated control animals. Comp ared with control rats infused with aCSF, GDNF infusion significantly decre ased the TBI-induced neuronal loss in both the CA2 (58%, p < 0.05) and CA3 regions (51%, P < 0.05). There was no difference in the number of GFAP-posi tive astroglial cells in the GDNF-infused rats in the TBI and sham-operated groups compared with the respective vehicle-treated groups. Conclusions. The authors found that GDNF treatment following TBI is neuropr otective.