Jensen F E
Department of Neurology, Children's Hospital, Boston, MA 02115, USA.
Ital J Neurol Sci. 1995 Feb-Mar;16(1-2):59-68. doi: 10.1007/BF02229075.
Clinically, neonatal hypoxic encephalopathy is commonly associated with seizure activity. Here we describe a rodent model of cerebral hypoxia in which there is are age dependent effects of hypoxia, with hypoxia inducing seizure activity in the immature rat, but not in the adult. Global hypoxia (3-4% O2) induced acute seizure activity during a window of development between postnatal day (P5-17), peaking at P10-12. Animals which had been rendered hypoxic between P10-12 had long term decreases in seizure threshold, while animals exposed at younger (P5) or older (P60) ages did not. Antagonists of excitatory amino acid (EAA) transmission appear to be superior to benzodiazepines in suppressing the acute and long term effects of perinatal hypoxia, suggesting involvement of the EAA system in these phenomena. No significant histologic damage occurs in this model, suggesting that functional alterations take place in neurons when exposed to an hypoxic insult at a critical developmental stage. Future work is directed at evaluating molecular and cellular events underlying the permanent increase in seizure susceptibility produced by this model.
临床上，新生儿缺氧缺血性脑病通常与癫痫活动相关。在此我们描述一种脑缺氧的啮齿动物模型，其中缺氧存在年龄依赖性效应，缺氧在未成熟大鼠中诱导癫痫活动，但在成年大鼠中则不会。整体缺氧（3 - 4% O₂）在出生后第5至17天的发育窗口期内诱导急性癫痫活动，在出生后第10至12天达到峰值。在出生后第10至12天期间缺氧的动物，其癫痫阈值长期降低，而在较年幼（出生后第5天）或较年长（出生后第60天）时暴露于缺氧的动物则没有这种情况。兴奋性氨基酸（EAA）传递拮抗剂在抑制围产期缺氧的急性和长期效应方面似乎优于苯二氮䓬类药物，这表明EAA系统参与了这些现象。在该模型中未发生明显的组织学损伤，这表明在关键发育阶段暴露于缺氧损伤时，神经元会发生功能改变。未来的工作旨在评估该模型所产生的癫痫易感性永久性增加背后的分子和细胞事件。
