INCREASED EXPRESSION OF GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR IN RAT BRAIN AFTER TRAUMATIC BRAIN INJURY

Abstract

Glial cell line-derived neurotrophic factor (GDNF) plays important roles not only for the differentiation of neurons during normal development but also for the survival and recovery of many populations of mature neurons. The effect of traumatic brain injury (TBI) on the expression of GDNF is currently unknown. To determine if there is alteration in GDNF after TBI we examined the effect of controlled cortical impact (CCI) injury on GDNF protein levels at 6 hours, 1 day, 1 week, and 4 weeks following injury by utilizing a commercially available antibody specific to GDNF. Rats were anesthetized and surgically prepared for CCI injury (4 m/sec, 2.7 mm) and sham surgery. Injured and sham animals (n=6 per group) were sacrificed at 6 hours, 1 day, 1 week, and 4 weeks and perfused with 4% paraformaldehyde. Coronal sections (35 mm thick) were cut through the hippocampus. An increased expression of GDNF protein was observed by immunohistochemistry in the dentate gyrus of hippocampus and the cortex in injured rats compared to sham controls. The increased expression of GDNF was more evidently observed in the ipsilateral dentate gyrus and the area around the contusion in the cortex. In the cortex, GDNF immunoreactivity appeared greatest in cells with glial morphology but in the hippocampus, GDNF immunoreactivity was greatest in neuronal-like cells. These changes were observed at 1 day, 1 and 4 weeks postinjury. We speculate that the up-regulation of the GDNF protein may reflect its neurotrophic and neuroprotective effect on dopaminergic system responding to the TBI insult.