创伤性窒息脑损害引起的迟发性LTP抑制及L-NNA对其影响

Delayed inhibition of long-term potentiation following traumatic asphyxia-induced cerebral impairment: effects of L-NNA, an inhibitor of NO synthases

目的 研究创伤性窒息 (TA)脑损害后长时程增强 (LTP)的变化以及一氧化氮合酶抑制剂L NNA对它的影响。方法 创伤性窒息后第 1天和第 3天分别记录海马Schaffer侧支 CA1和穿通通路 齿状回突触的群体峰电位。结果 在海马侧支 CA1通路 ,脑损害后第 1天和第 3天LTP明显受到抑制 ,第 1天和第 3天LTP受抑制程度无明显不同。穿通质 齿状回通路中LTP仅在脑损害后第 3天受到明显抑制。给予L NNA (5 0mg/kgi p )可显著减轻LTP迟发性的抑制。以上结果表明海马系统的LTP在TA后明显受到损害 ,海马神经元存在一个可称之为“迟发性LTP抑制”的现象。结论 一氧化氮合酶抑制剂L NNA可减轻LTP的损害和迟发性抑制作用。提示NO参予了迟发性LTP抑制的病理发生机制 ,且可能与创伤性窒息脑损害后的学习、记忆能力减退有关。

Objective The present study was the first to investigate the changes of long term potentiation in vivo occurring after traumatic asphyxia induced cerebral impairment, and effects of nitric oxide synthase inhibitor L NNA.Methods LTP was significantly depressed after traumatic asphyxia. In Schaffer CA1 pathways, the inhibition of LTP was obvious at first and third day after traumatic asphyxia. In perforant path dentate gyrus synapses, LTP was substantially inhibited only at third day after traumatic asphyxia, and the changes of LTP at third day differed from inhibition of the first day. Treatment with L NNA (50mg/kg,i.p.) significantly attenuated the inhibition of LTP.Results This study showed that the LTP of hippocampal system was substantially suppressed after traumatic asphyxia, a so called “delayed inhibition” of LTP induction existed in the hippocampal neurons. Conclusions The result agrees with some clinic patients symptoms of memory disturbance. L NNA could reduce the inhibition of LTP. The effects of L NNA suggests that NO play a crucial role in delayed inhibition of LTP and may be involves in the memory defects that occur subsequent to traumatic asphyxia.