Cyclosporin ameliorates traumatic brain-injury-induced alterations of hippocampal synaptic plasticity

Although traumatic brain injury (TBI) often results in impaired learning an d memory functions, the underlying mechanisms are unknown and there are cur rently no treatments that can preserve such functions. We studied plasticit y at CA3-CA1 synapses in hippocampal slices from rats subjected to controll ed cortical impact TBI. Long-term potentiation (LTP) of synaptic transmissi on was markedly impaired, whereas long-term depression (LTD) was enhanced, 48 h following TBI when compared to unoperated and sham control rats. Post- TBI administration of cyclosporin A, a compound that stabilizes mitochondri al function, resulted in a highly significant amelioration of the impairmen t of LTP and completely prevented the enhancement of LTD. Our data suggest that alterations in hippocampal synaptic plasticity may be responsible for learning and memory deficits resulting from TBI and that agents such as cyc losporin A that stabilize mitochondrial function may be effective treatment s for TBI. (C) 2000 Academic Press.