Fukushima R, Yoshida Y, Chiba S
Department of Psychiatry and Neurology, Asahikawa Medical College, Japan.
Yakubutsu Seishin Kodo. 1990 Sep;10(3):335-42.
Perinatal hypoxia is known as a risk factor for human epilepsies. Previous studies in our laboratory have shown that the rats with postnatal hypoxia show facilitation of the kindling formation and enhanced susceptibility to pentylenetetrazol (PTZ)-induced seizures even after the maturation. In the present study, the effects of postnatal hypoxia (100% N2, for approximately 5 min, at ten days of age) on monoamine and amino acid levels in the brain of adult rats (three months of age) were investigated to clarify the biochemical basis of the enhanced seizure susceptibility. In the hypoxia-treated rats, norepinephrine (NE) was significantly decreased in the pons-medulla (82% of control) and hypothalamus (85%) as compared with controls. Dopamine (DA) was decreased in the pons-medulla (83%). A decrease in DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was also noted in the substantia nigra (71%) and hippocampus (64%), respectively. On the other hand, gamma-aminobutyric acid (GABA) was significantly increased in the striatum (121%). These findings indicate that the enhanced seizure susceptibility in these rats may be attributed to 1) impaired development of noradrenergic and dopaminergic neurons, of which these transmissions are known as inhibitory modulators of seizure discharge in some animal models of epilepsies, and 2) changes of GABAergic and dopaminergic transmissions in the striato-nigral pathway, which is a wellknown regulation system for seizure propagation.
围产期缺氧是人类癫痫的一个危险因素。我们实验室之前的研究表明，出生后缺氧的大鼠即使在成熟后，点燃形成也会加速，对戊四氮（PTZ）诱导的癫痫发作的易感性也会增强。在本研究中，研究了出生后缺氧（100%氮气，约5分钟，出生后10天）对成年大鼠（3个月大）大脑中单胺和氨基酸水平的影响，以阐明癫痫易感性增强的生化基础。与对照组相比，缺氧处理的大鼠脑桥-延髓中的去甲肾上腺素（NE）显著降低（为对照组的82%），下丘脑降低（为对照组的85%）。脑桥-延髓中的多巴胺（DA）降低（为对照组的83%）。黑质（为对照组的71%）和海马体（为对照组的64%）中DA代谢产物3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）也分别减少。另一方面，纹状体中的γ-氨基丁酸（GABA）显著增加（为对照组的121%）。这些发现表明，这些大鼠癫痫易感性增强可能归因于：1）去甲肾上腺素能和多巴胺能神经元发育受损，在一些癫痫动物模型中，这些神经传递被认为是癫痫放电的抑制性调节因子；2）纹状体-黑质通路中GABA能和多巴胺能神经传递的变化，这是一个众所周知的癫痫传播调节系统。
