Jensen M S, Lambert J D, Johansen F F
Institute of Physiology, University of Aarhus, Denmark.
Brain Res. 1991 Jul 19;554(1-2):166-75. doi: 10.1016/0006-8993(91)90185-x.
Pyramidal neurons in area CA1 of the septal hippocampus degenerate 2-3 days after an episode of transient global cerebral ischemia. The purpose of this study was to investigate synaptic transmission and passive neuronal properties in the post-ischemic period prior to neuronal death. Electrophysiological recordings were made from area CA1 in hippocampal slices prepared from rats which had survived a period of 20 min of ischemia for up to 5 days. In septal slices, field responses were in area CA1 unaltered up to 24 h after the ischemic insult. Forty-eight hours after ischemia, the mean amplitude of the population spike, but not the field-EPSP, was significantly reduced. In septal slices prepared more than 48 h after ischemia field potentials were absent or strongly attenuated, whereas they were intact in slices prepared from the temporal pole. No spontaneous discharges were detected in slices prepared at any time from post-ischemic rats. Intracellular recordings were obtained from slices up to 48 h after the ischemic episode. There was no significant difference in the resting membrane potential or input resistance between these neurons and those from control slices. Action potentials followed by a fast afterhyperpolarization and spike accommodation were preserved in all post-ischemic neurons. In all neurons investigated, orthodromic stimulation evoked an EPSP followed by a fast- and then a slow-IPSP. One hour after ischemia, the slow-IPSP was reduced. Forty-eight hours after ischemia, the fast-IPSP was significantly increased. The EPSP was markedly attenuated by the non N-methyl-D-aspartate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM). The residual depolarizing component was amplified by perfusing with Mg(2+)-free medium and blocked by the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid. Paired-pulse facilitation of the EPSP was also preserved. As in control slices, the slow-IPSP and paired-pulse depression of the fast-IPSP were blocked by 1 microM baclofen. The present experiments provide no evidence that overt alteration of excitatory synaptic transmission or neuronal properties favouring hyperexcitability precede the ischemically induced death of CA1 pyramidal cells.
短暂性全脑缺血发作后2 - 3天，隔区海马CA1区的锥体神经元发生退化。本研究的目的是调查神经元死亡前缺血后时期的突触传递和被动神经元特性。对经历20分钟缺血达5天的大鼠制备的海马切片CA1区进行电生理记录。在隔区切片中，缺血损伤后24小时内CA1区的场反应未改变。缺血48小时后，群体锋电位的平均幅度显著降低，但场兴奋性突触后电位（field-EPSP）未降低。缺血48小时后制备的隔区切片中无场电位或场电位强烈衰减，而颞叶极区制备的切片中场电位完整。在缺血后大鼠任何时间制备的切片中均未检测到自发放电。在缺血发作后48小时内从切片获得细胞内记录。这些神经元与对照切片的神经元在静息膜电位或输入电阻上无显著差异。所有缺血后神经元均保留动作电位后跟随快速超极化后电位和锋电位适应。在所有研究的神经元中，顺向刺激诱发兴奋性突触后电位，随后是快速抑制性突触后电位（fast-IPSP）和慢速抑制性突触后电位（slow-IPSP）。缺血1小时后，慢速抑制性突触后电位降低。缺血48小时后，快速抑制性突触后电位显著增加。非N-甲基-D-天冬氨酸受体阻断剂6-氰基-7-硝基喹喔啉-2,3-二酮（10 microM）可使兴奋性突触后电位明显衰减。通过用无镁培养基灌注可放大残余的去极化成分，并被N-甲基-D-天冬氨酸受体拮抗剂DL-2-氨基-5-磷酸戊酸阻断。兴奋性突触后电位的双脉冲易化也得以保留。与对照切片一样，1 microM巴氯芬可阻断慢速抑制性突触后电位和快速抑制性突触后电位的双脉冲抑制。本实验没有提供证据表明在CA1锥体细胞缺血诱导死亡之前，兴奋性突触传递或有利于兴奋性过高的神经元特性有明显改变。
