Zhao Shi-gang, Jiang Yu-wu, Luo Qiang, Wu Xi-ru
Division of Neurology, Department of Pediatrics, First Hospital, Beijing University, Beijing 100034, China.
Zhonghua Er Ke Za Zhi. 2003 Jan;41(1):21-4.
To investigate the functional role of hippocampal mossy fiber sprouting in the pathophysiologic mechanism of initiation and propagation of epilepsy.
The authors examined hippocampal mossy fiber synaptic reorganization and the changes of hippocampal neurons in P77PMC rats at different stages in the course of recurrent seizures using Timm's method of silver sulfide staining and Nissl staining and observed the effects of recurrent audiogenic seizures (AGSs) on seizure behavior of P77PMC rats.
Frequent recurrent AGSs could cause neuronal loss in CA(1) region of hippocampus and hippocampal mossy fiber sprouting got into the inner molecular layer of dentate gyrus in P77PMC rats, and could decrease the latency of IV/V grade of AGSs, increase the durations of AGSs. The mean A of CA(1) region of hippocampus in Nissl staining after 50 times of AGSs was 35.3 +/- 0.8, which was markedly lower than that of the control (44.1 +/- 0.5; F = 333.89, P < 0.001). The mean A of the inner molecular layer of dentate gyrus in Timm's staining after 50 times of AGSs was 49.3 +/- 4.6, which was markedly higher than that of the control (26.8 +/- 1.7; F = 76.83, P < 0.001). After 30 and 50 times of AGSs, the latent periods of IV/V grade of AGSs were 12 +/- 8 (t = 3.805; P < 0.02) and 17 +/- 7 (t = 5.927; P < 0.002) seconds shorter than the initial period of stimulation respectively on average, and the durations of AGSs were 19 +/- 18 (t = 2.644; P < 0.05) and 10 +/- 7 (t = 3.780; P < 0.02) seconds longer.
Hippocampal mossy fiber sprouting and neuronal loss not only presents in limbic seizure, but also in AGS, the seizure can be initiated in brainstem but rapidly generalized;in AGS-prone rats, recurrent AGSs can cause mossy fiber synaptic reorganization and neuronal loss in hippocampus, and can also enhance seizure susceptibility of P77PMC rats. In the course of recurrent AGSs, enhanced seizure susceptibility happened before hippocampal mossy fiber sprouting. Their temporal relationships indicate that the anatomical changes may be preceded by functional changes of elevated excitability in the brain.
探讨海马苔藓纤维出芽在癫痫起始和传播的病理生理机制中的作用。
作者采用硫化银染色的Timm法和尼氏染色法，检测复发性癫痫发作过程中不同阶段P77PMC大鼠海马苔藓纤维突触重组及海马神经元的变化，并观察复发性听源性癫痫发作（AGS）对P77PMC大鼠癫痫行为的影响。
频繁的复发性AGS可导致P77PMC大鼠海马CA(1)区神经元丢失，海马苔藓纤维出芽进入齿状回内分子层，并可缩短AGSⅣ/Ⅴ级发作的潜伏期，延长AGS发作的持续时间。50次AGS发作后尼氏染色显示海马CA(1)区的平均A值为35.3±0.8，明显低于对照组（44.1±0.5；F = 333.89，P < 0.001）。50次AGS发作后Timm染色显示齿状回内分子层的平均A值为49.3±4.6，明显高于对照组（26.8±1.7；F = 76.83，P < 0.001）。30次和50次AGS发作后，AGSⅣ/Ⅴ级发作的潜伏期分别比刺激初始期平均缩短12±8（t = 3.805；P < 0.02）和17±7（t = 5.927；P < 0.002）秒，AGS发作的持续时间分别延长19±18（t = 2.644；P < 0.05）和10±7（t = 3.780；P < 0.02）秒。
海马苔藓纤维出芽和神经元丢失不仅存在于边缘性癫痫发作中，也存在于AGS中，癫痫可起源于脑干但迅速泛化；在易患AGS的大鼠中，复发性AGS可导致海马苔藓纤维突触重组和神经元丢失，还可增强P77PMC大鼠的癫痫易感性。在复发性AGS过程中，癫痫易感性增强发生在海马苔藓纤维出芽之前。它们的时间关系表明，解剖学变化可能先于大脑中兴奋性升高的功能变化。
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