Urban L, Neill K H, Crain B J, Nadler J V, Somjen G G
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710.
J Neurosci. 1989 Nov;9(11):3966-75. doi: 10.1523/JNEUROSCI.09-11-03966.1989.
After transient forebrain ischemia in the Mongolian gerbil, CA1b hippocampal pyramidal cells degenerate during a period of 2-4 d. We tested the hypothesis that this delayed neuronal death is preceded by excessive synaptic excitation. Hippocampal slices were prepared from gerbils that had been subjected to a 5 min occlusion of both common carotid arteries. Input/output curves demonstrated enhancement of the initial slope of the Schaffer collateral-commissural focally recorded EPSP at all stimulus currents between 5 and 10 hr after the ischemic insult. The duration of the focally recorded EPSP also increased. At the same time, the excitability of the CA1b pyramidal cells decreased. Thus, the EPSP brought fewer pyramidal cells to threshold than the same size EPSP in control slices. During the first 14 hr after ischemia, the antidromic population spike remained unaffected. By 24 hr after ischemia, however, the focally recorded EPSP and both orthodromic and antidromic population spikes were markedly depressed, and they declined further over the next 2 d. No recovery was detected. In the same slices, transient ischemia only mildly and reversibly affected the response of dentate granule cells to perforant path stimulation and did not affect their response to antidromic stimulation. Hippocampal slices adjacent to those used for electrophysiological recording were analyzed histologically. Examination of somatic argyrophilia confirmed that CA1b pyramidal cells suffered delayed neuronal death, whereas dentate granule cells remained intact. Pyramidal cell argyrophilia was, however, not detected until 2 d after these neurons had become virtually inexcitable. We conclude that CA1b pyramidal cells begin to lose electrophysiological function well before definite morphological signs of degeneration become visible. The observation of enhanced excitatory transmission 5-10 hr after reperfusion is consistent with the idea that delayed ischemic neuronal death results, at least in part, from excessive excitation.
蒙古沙鼠短暂性前脑缺血后，CA1b海马锥体细胞在2 - 4天内发生退化。我们检验了这样一个假说，即这种延迟性神经元死亡之前存在过度的突触兴奋。从经历了5分钟双侧颈总动脉闭塞的沙鼠制备海马切片。输入/输出曲线显示，在缺血性损伤后5至10小时之间的所有刺激电流下，局部记录的Schaffer侧支-联合通路兴奋性突触后电位（EPSP）的初始斜率增强。局部记录的EPSP持续时间也增加。与此同时，CA1b锥体细胞的兴奋性降低。因此，与对照切片中相同大小的EPSP相比，该EPSP使达到阈值的锥体细胞数量减少。在缺血后的前14小时内，逆行性群体峰电位未受影响。然而，缺血后24小时，局部记录的EPSP以及顺行性和逆行性群体峰电位均明显降低，并在接下来的2天内进一步下降。未检测到恢复。在同一切片中，短暂性缺血仅对齿状颗粒细胞对穿通路径刺激的反应产生轻微且可逆的影响，而不影响其对逆行刺激的反应。对用于电生理记录的切片相邻的海马切片进行组织学分析。对体细胞嗜银性的检查证实，CA1b锥体细胞遭受延迟性神经元死亡，而齿状颗粒细胞保持完整。然而，直到这些神经元几乎失去兴奋性2天后才检测到锥体细胞嗜银性。我们得出结论，在明确的退化形态学迹象可见之前，CA1b锥体细胞就开始丧失电生理功能。再灌注后5 - 10小时兴奋性传递增强的观察结果与延迟性缺血性神经元死亡至少部分是由过度兴奋导致的观点一致。
