Prophylactic effects of hypothermia and general anesthetics against anoxia in rat hippocampal slices in vitro

尽管先前的临床报告表明，低温和/或全身麻醉剂对脑缺血有预防作用，但低温和/或全身麻醉剂保护脑组织免受缺氧的细胞机制尚不清楚。本研究采用体外大鼠海马切片制备，利用电生理技术研究了低温和全麻对缺氧的影响。采用细胞外记录法记录大鼠海马CA1锥体神经元的场电位。切片置于液/气界面，灌注95%O_2/5%CO_2和人工脑脊液（37℃）。在没有低温（27℃）和/或全身麻醉剂（硫喷妥钠、异丙酚、挥发性麻醉剂）的情况下，通过将95% o2 /5% co_2的气体混合物切换为95% n2 /5% co_2，对切片进行缺氧（0%氧气）。37℃无全麻条件下180秒缺氧诱导海马缺氧去极化（AD）由于NMDA、非NMDA和GABA受体拮抗剂联合使用不能预防AD，因此突触传递不是引发AD的原因。使用硫喷妥，而不是异丙酚和挥发性麻醉剂，可以显著降低AD的发病率。单独的低温降低了AD的发病率，并加速了硫喷妥钠的降低。本研究清楚地表明，低温和/或硫喷妥钠治疗可以预防AD，并对体外海马切片制剂的缺血产生预防作用。

Although previous clinical reports suggested the prophylactic effects of hypothermia and/or general anesthetics against cerebral ischemia, the cellular mechanisms by which hypothermia and/or anesthetics protect brain tissue against hypoxia remain unknown. In the present study, we have employed the rat hippocampal slice preparations in vitro, and studied the effects of hypothermia and general anesthetics against anoxia using electrophysiological techniques.Extracellular recordings were used to record field potentials in CA1 pyramidal neurons of rat hippocampal slices. Slices were placed on a liquid/gas interface, and were perfused with 95%O_2/5%CO_2 and artificial cerebrospinal fluid (37℃). Anoxia (0% oxygen) was applied to slices by switching the gas mixture from 95%O_2/5%CO_2 to 95%N_2/5%CO_2 in the absence and presence of hypothermia (27℃) and/or general anesthetics (thiopental, propofol, volatile anesthetics).The 180-sec anoxia induced anoxic depolarization (AD) in hippocampal slices at 37℃ in the absence of general anesthetics. Since combination of the NMDA, non-NMDA, and GABA receptor antagonists failed to prevent AD, synaptic transmission is not responsible for elicitation of AD. The treatment with thiopental, but not propofol and volatile anesthetics, significantly reduced the incidence of AD. The hypothermia alone reduced the incidence of AD, and accelerated the reduction in the presence of thiopental.The present study clearly demonstrated that the treatment with hypothermia and/or thiopental prevent AD, and produce prophylactic actions against ischemia in hippocampal slice preparations in vitro.