41 Neurotrophins and stroke

Recent studies have made signiiicant advances in our understanding of the responses of specific neurotrophins to experimc~ttal traumatic brain injury in the rat Cortical impact injury produces transxnt increases in c-la mRNA expression which begins as early as five minutes after injury and subsides by one day after injury in tbc cerebral cortex ipsilateral to injury. In addition, A&l transcription factor binding is greatly increased in the injured cerebral cortex at one hour, three hours and five hours past-injury. AP-1 binding remains incrclased for at least one day after injury, while SP-1 transcription factor binding activity does not increase. Additional stud& have confnned increases in levels of c-foe mRNA expression in the hippocampus at 30 minutes, one hour and three hours after injury. These increases in c-fos mRNA in the hippocampus preceded increased levels of NGF mRNA dctectcd at one hour and three hours but not at 30 minutes following inJury. These data are consistent with the possible regulatory role of cndogenwus c-fos on NGF expression following traumatic brain injury. Studies have also detected BDNF mRNA increases at one, three, and five hours after unilateral cortical injury in the cortex ipsilatcral to the injury site and bilaterally in the dorsal hippocampus. NT3 mRNA did not change significantly, suggesting that increased levels of BDNF mRNA rather than NT3 are components of pathophysiologlcal responses to traumatic brain injury. Finally, recent in virro models of traumatic brain injury have provided evidence that neumtrophic proteins can enhance the rccovcry of neuronal cytoskeleton. Thus, ncurotrophm-based therapy could employ either administration of exogenous ncurotrophic proteins andior transfection of cDNA for appropriate neurotropbins NEUROTROPHINS AND STROKE