Wasterlain C G, Fujikawa D G, Penix L, Sankar R
Epilepsy Research Laboratory Veterans Affairs Medical Center, Sepulveda, CA 91343.
Epilepsia. 1993;34 Suppl 1:S37-53. doi: 10.1111/j.1528-1157.1993.tb05905.x.
Human status epilepticus (SE) is consistently associated with cognitive problems, and with widespread neuronal necrosis in hippocampus and other brain regions. In animal models, convulsive SE causes extensive neuronal necrosis. Nonconvulsive SE in adult animals also leads to widespread neuronal necrosis in vulnerable regions, although lesions develop more slowly than they would in the presence of convulsions or anoxia. In very young rats, nonconvulsive normoxic SE spares hippocampal pyramidal cells, but other types of neurons may not show the same resistance, and inhibition of brain growth, DNA and protein synthesis, and of myelin formation and of synaptogenesis may lead to altered brain development. Lesions induced by SE may be epileptogenic by leading to misdirected regeneration. In SE, glutamate, aspartate, and acetylcholine play major roles as excitatory neurotransmitters, and GABA is the dominant inhibitory neurotransmitter. GABA metabolism in substantia nigra (SN) plays a key role in seizure arrest. When seizures stop, a major increase in GABA synthesis is seen in SN postictally. GABA synthesis in SN may fail in SE. Extrasynaptic factors may also play an important role in seizure spread and in maintaining SE. Glial immaturity, increased electronic coupling, and SN immaturity facilitate SE development in the immature brain. Major increases in cerebral blood flow (CBF) protect the brain in early SE, but CBF falls in late SE as blood pressure falters. At the same time, large increases in cerebral metabolic rate for glucose and oxygen continue throughout SE. Adenosine triphosphate (ATP) depletion and lactate accumulation are associated with hypermetabolic neuronal necrosis. Excitotoxic mechanisms mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors open ionic channels permeable to calcium and play a major role in neuronal injury from SE. Hypoxia, systemic lactic acidosis, CO2 narcosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, pulmonary edema, acute renal tubular necrosis, high output failure, aspiration pneumonia, hyperpyrexia, blood leukocytosis and CSF pleocytosis are common and potentially serious complications of SE. Our improved understanding of the pathophysiology of brain damage in SE should lead to further improvement in treatment and outcome.
人类癫痫持续状态（SE）始终与认知问题以及海马体和其他脑区广泛的神经元坏死相关。在动物模型中，惊厥性SE会导致广泛的神经元坏死。成年动物的非惊厥性SE也会导致易损区域广泛的神经元坏死，尽管病变发展比惊厥或缺氧时更为缓慢。在非常年幼的大鼠中，非惊厥性常氧SE可使海马体锥体细胞免受损伤，但其他类型的神经元可能不具有同样的抗性，并且对脑生长、DNA和蛋白质合成以及髓鞘形成和突触形成的抑制可能导致脑发育改变。SE诱导的损伤可能通过导致再生方向错误而具有致痫性。在SE中，谷氨酸、天冬氨酸和乙酰胆碱作为兴奋性神经递质起主要作用，而GABA是主要的抑制性神经递质。黑质（SN）中的GABA代谢在癫痫发作终止中起关键作用。癫痫发作停止时，发作后SN中GABA合成会大幅增加。SE中SN的GABA合成可能会失败。突触外因素在癫痫发作传播和维持SE方面也可能起重要作用。神经胶质细胞不成熟、电耦合增加和SN不成熟促进了未成熟脑SE的发展。早期SE时脑血流量（CBF）大幅增加可保护大脑，但随着血压下降，晚期SE时CBF会下降。与此同时，整个SE过程中脑葡萄糖和氧代谢率持续大幅增加。三磷酸腺苷（ATP）耗竭和乳酸积累与代谢亢进性神经元坏死相关。由N-甲基-D-天冬氨酸（NMDA）和非NMDA谷氨酸受体介导的兴奋性毒性机制会打开对钙通透的离子通道，并在SE导致的神经元损伤中起主要作用。缺氧、全身性乳酸酸中毒、二氧化碳麻醉、高钾血症、低血糖、休克、心律失常、肺水肿、急性肾小管坏死、高输出量衰竭、吸入性肺炎、高热、血白细胞增多和脑脊液细胞增多是SE常见且可能严重的并发症。我们对SE中脑损伤病理生理学的深入理解应会带来治疗和预后的进一步改善。
