Albensi B C, Sullivan P G, Thompson M B, Scheff S W, Mattson M P
Sanders-Brown Research Center on Aging and Department of Anatomy & Neurobiology, University of Kentucky, Lexington, Kentucky 40536, USA.
Exp Neurol. 2000 Apr;162(2):385-9. doi: 10.1006/exnr.1999.7338.
Although traumatic brain injury (TBI) often results in impaired learning and memory functions, the underlying mechanisms are unknown and there are currently no treatments that can preserve such functions. We studied plasticity at CA3-CA1 synapses in hippocampal slices from rats subjected to controlled cortical impact TBI. Long-term potentiation (LTP) of synaptic transmission 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 mitochondrial function, resulted in a highly significant amelioration of the impairment 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 cyclosporin A that stabilize mitochondrial function may be effective treatments for TBI.
尽管创伤性脑损伤（TBI）常导致学习和记忆功能受损，但其潜在机制尚不清楚，目前也没有能够保留这些功能的治疗方法。我们研究了遭受可控皮质撞击性TBI的大鼠海马切片中CA3-CA1突触的可塑性。与未手术和假手术对照大鼠相比，TBI后48小时，突触传递的长时程增强（LTP）明显受损，而长时程抑制（LTD）增强。TBI后给予环孢素A（一种稳定线粒体功能的化合物），可显著改善LTP的损伤，并完全阻止LTD的增强。我们的数据表明，海马突触可塑性的改变可能是TBI导致学习和记忆缺陷的原因，而像环孢素A这样稳定线粒体功能的药物可能是治疗TBI的有效方法。
