Somjen G G, Aitken P G, Balestrino M, Herreras O, Kawasaki K
Division of Physiology, Duke University Medical Center, Durham, N.C. 27710.
Stroke. 1990 Nov;21(11 Suppl):III179-83.
If oxygen is withdrawn from rat hippocampal slices, a spreading depression-like response occurs earlier and is of larger amplitude in the CA1 area than in the dentate gyrus. After reoxygenation, recovery of synaptic transmission correlates inversely with the time spent in spreading depression. Recovery occurs more frequently in dentate gyrus than in CA1. Chlorpromazine and the gangliosides GM1 and AGF2 promote recovery from hypoxic depression of synaptic transmission in CA1. Prevention of irreversible loss of function correlates closely with a shortening of the time spent in spreading depression. If Ca2+ is withdrawn before hypoxia, then synaptic function recovers upon restoration of oxygen and [Ca2+]o, despite prolonged spreading depression. When spreading depression lasting more than 6-9 minutes is induced in fully oxygenated slices by superfusion with high-K+ solution, then transient recovery is followed by long-lasting loss of synaptic function. In intact brain of anesthetized rats, synaptic transmission in CA1 recovers after spreading depression-like depolarization lasting more than 30 minutes, but is lost irreversibly after 60 minutes. We conclude that entry of Ca2+ into neurons caused by spreading depression-like depolarization is important in the selective vulnerability of neurons; the duration of depolarization is critical to cell survival; and in the presence of a normal blood supply, neurons resist protracted spreading depression-like depolarization.
如果从大鼠海马切片中撤除氧气，那么在CA1区会比齿状回更早出现类似扩散性抑制的反应，且振幅更大。再给氧后，突触传递的恢复与处于扩散性抑制状态的时间呈负相关。齿状回比CA1区更频繁地出现恢复。氯丙嗪以及神经节苷脂GM1和AGF2可促进CA1区突触传递从缺氧抑制状态中恢复。防止功能的不可逆丧失与缩短处于扩散性抑制状态的时间密切相关。如果在缺氧前撤除Ca2+，那么尽管扩散性抑制持续时间延长，但在恢复氧气和[Ca2+]o后突触功能仍可恢复。当用高钾溶液灌流在完全氧合的切片中诱导出持续超过6 - 9分钟的扩散性抑制时，随后会出现短暂恢复，接着是突触功能的持久丧失。在麻醉大鼠的完整大脑中，CA1区的突触传递在持续超过30分钟的类似扩散性抑制的去极化后可恢复，但在60分钟后会不可逆地丧失。我们得出结论，类似扩散性抑制的去极化所导致的Ca2+进入神经元在神经元的选择性易损性中起重要作用；去极化的持续时间对细胞存活至关重要；并且在有正常血液供应的情况下，神经元能够抵抗长时间的类似扩散性抑制的去极化。
