Jensen F E, Blume H, Alvarado S, Firkusny I, Geary C
Department of Neurology, Children's Hospital, Boston, Massachusetts, USA.
Epilepsia. 1995 Oct;36(10):966-72. doi: 10.1111/j.1528-1157.1995.tb00954.x.
Clinically, and in experimental models, perinatal hypoxic encephalopathy is commonly associated with seizures. We previously described a rat model in which hypoxia induces seizures and permanently increases in seizure susceptibility in immature rats [postnatal day (P) 10-12] but not in older rats. In the present study, we compared the effect of pretreatment with the excitatory amino acid antagonists MK-801 and NBQX versus lorazepam in our rat model of perinatal hypoxia. Animals exposed to hypoxia at P10 without treatment have frequent seizures during hypoxia and subsequently exhibit increased seizure susceptibility to flurothyl. Treatment with 6-nitro-7-sulfamoylbenzo(f)quinoxaline-2,3-dione (NBQX 20 mg/kg) effectively suppressed hypoxia-induced seizures in immature rats and also protected against permanent changes in flurothyl threshold in adulthood, whereas treatment with MK-801 (1 mg/kg) or lorazepam (LZP 1 mg/kg) did not prevent these hypoxia-related epileptogenic effects. These results suggest that activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA) receptors may partly mediate the age-dependent epileptogenic effect of hypoxia in the perinatal period.
临床上以及在实验模型中，围产期缺氧性脑病通常与癫痫发作相关。我们之前描述了一种大鼠模型，其中缺氧会诱发癫痫发作，并使未成熟大鼠（出生后第10 - 12天）的癫痫易感性永久性增加，但对成年大鼠则无此影响。在本研究中，我们比较了在我们的围产期缺氧大鼠模型中，用兴奋性氨基酸拮抗剂MK - 801和NBQX预处理与用劳拉西泮预处理的效果。在出生后第10天暴露于缺氧且未接受治疗的动物，在缺氧期间频繁出现癫痫发作，随后对氟烷的癫痫易感性增加。用6 - 硝基 - 7 - 氨磺酰基苯并(f)喹喔啉 - 2,3 - 二酮（NBQX 20 mg/kg）治疗可有效抑制未成熟大鼠缺氧诱导的癫痫发作，并且还能预防成年期氟烷阈值的永久性变化，而用MK - 801（1 mg/kg）或劳拉西泮（LZP 1 mg/kg）治疗并不能预防这些与缺氧相关的致痫作用。这些结果表明，α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸（AMPA）受体的激活可能部分介导了围产期缺氧的年龄依赖性致痫作用。
