Abstract for presentation at 6th World Congress on Brain Injury

Introduction: Neurotrophin expression in the rat hippocampus is altered by experimental TBI and neurotrophins are neuroprotective. Glucocorticoids are regulators of brain neurotrophin levels and are often prescribed following TBI, although clear evidence of benefit is lacking. Aim: To determine the effects of alterations of the glucocorticoid status on neurotrophin expression in the hippocampus and on outcome after traumatic brain injury (TBI). Methods: Fluid percussion injury (FPI) in adrenal-intact or adrenalectomised (ADX) rats with or without corticosterone replacement. In-situ hybridisation was used to assess hippocampal neurotophin expression. Cognitive outcome was determined using the T-Maze test. Histological outcome was measured by counts of normal, necrotic and apoptotic neurones in the hippocampus on H&E sections. The mode of neuronal death was assessed using cresyl violet sections, the TUNEL technique and immunohistochemistry for apoptotic markers. Results: NGF and BDNF mRNA expression were increased in the hippocampus by FPI (ANOVA, p<0.05). Prior ADX obliterated the NGF response to FPI (p<0.0001) but enhanced the BDNF response (p<0.05). NT-3 mRNA expression was decreased by FPI (p<0.0001) and further reduced by ADX (p=0.0009). neurones in the hippocampal CA3/2 region and the hilus of the dentate gyrus (DG) underwent non-apoptotic cellular death after FPI associated with a significant impairment of T-Maze performance (p=0.03). ADX caused apoptotic neuronal loss in the DG, which was not associated with a deficit in the T-Maze function. Prior ADX did not significantly affect the histological or cognitive outcome after FPI. Conclusion: Glucocorticoids have a critical but paradoxical role in modulating the neurotrophin responses to TBI. Although ADX altered the trauma-induced neurotrophin response, it did not affect cognitive function or the degree of hippocampal neuronal loss. These results question the use of glucocorticoids after TBI.