Jensen F E, Wang C
Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Epilepsy Res. 1996 Dec;26(1):131-40. doi: 10.1016/s0920-1211(96)00049-6.
Hypoxia is the most common cause of neonatal seizures and encephalopathy. We have previously developed an in vivo experimental model of perinatal hypoxia which exhibits age-dependent acute and chronic epileptogenic effects. Between postnatal day (P) 10-12, the rat exhibits acute seizure activity during global hypoxia, while no seizures are induced at earlier (P5) or older (P60) ages. Rats exposed to hypoxia between P10-12 have reduced seizure thresholds to chemical convulsants in adulthood. The nonNMDA antagonists NBQX appears to suppress both the acute and long term epileptogenic effects of hypoxia. The age-dependency of the hyperexcitable response to hypoxia in vivo can be reproduced in vitro using hippocampal slices. In Mg(2+)-free media, hypoxia induced ictal discharges within 60 s of onset in 79% of slices from normal P10 rat pups compared to 11% of adult slices (p < 0.001). Model systems such as that described here allow for correlation of in vitro and in vivo electrophysiology and should provide data regarding the pharmacological and physiological characteristics of hypoxia-induced seizure activity in the immature brain which could ultimately be applied to therapeutic strategies.
缺氧是新生儿癫痫发作和脑病的最常见原因。我们之前建立了一种围产期缺氧的体内实验模型，该模型表现出年龄依赖性的急性和慢性致痫作用。在出生后第（P）10 - 12天，大鼠在全身性缺氧期间表现出急性癫痫发作活动，而在更早（P5）或更晚（P60）的年龄则不会诱发癫痫发作。在P10 - 12期间暴露于缺氧的大鼠成年后对化学惊厥剂的癫痫发作阈值降低。非NMDA拮抗剂NBQX似乎能抑制缺氧的急性和长期致痫作用。体内对缺氧的过度兴奋反应的年龄依赖性可以在体外使用海马切片进行重现。在无镁培养基中，缺氧在正常P10大鼠幼崽的79%的切片中发作起始后60秒内诱发发作性放电，而成年大鼠切片的这一比例为11%（p < 0.001）。本文所述的模型系统允许体外和体内电生理学的关联，并应提供有关未成熟大脑中缺氧诱导的癫痫发作活动的药理学和生理学特征的数据，这些数据最终可应用于治疗策略。
