Kubová Hana, Mares Pavel
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Epileptic Disord. 2007 Dec;9 Suppl 1:S36-43. doi: 10.1684/epd.2007.0150.
The effects of hypoxia on susceptibility to pentylenetetrazol (PTZ)-induced seizures were assessed in juvenile rats. Animals at postnatal (P) day 25 were exposed to hypobaric hypoxia (simulated altitude of 7000 m) for 8 h PTZ in a dose of 100 mg/kg was injected 1, 3 or 7 days later and latency, pattern and severity of seizures were registered. Mortality due to seizures was also evaluated. Two seizure types were evaluated: minimal mostly clonic seizures (mMS) and generalized tonic clonic seizures (GTCS). To study protective effects of vigabatrin (600 mg/kg, i.p.), drug was injected either 24 h before or immediately after hypoxia exposure. Non-hypoxic animals of corresponding age were used for comparison as controls. In non-hypoxic controls, administration of vigabatrin had pro-convulsive effects in intervals from 3 days up to 1 week - incidence of GTCS increased by 56-57%. Hypoxia exposure resulted to increased seizure susceptibility three days later, incidence of generalized tonic clonic seizures increased by 60% and latency to both seizure types shorter than in non-hypoxic controls. Also, mortality due to seizures was higher (by 58%). In other intervals, there was no difference between hypoxic and non-hypoxic animals. Vigabatrin administered 24 h before hypoxia led to significant decrease of seizure-induced mortality in intervals 1 and 3 days. Administration of vigabatrin immediately after hypoxia exposure resulted in decreased seizure severity when assessed 3 days later. Our data suggest that hypobaric hypoxia transiently increases seizure susceptibility. This effect is partially abolished by vigabatrin administered after hypoxia exposure.
在幼年大鼠中评估了缺氧对戊四氮（PTZ）诱导癫痫易感性的影响。出生后（P）第25天的动物暴露于低压缺氧（模拟海拔7000米）8小时，1、3或7天后注射剂量为100mg/kg的PTZ，并记录癫痫发作的潜伏期、模式和严重程度。还评估了癫痫发作导致的死亡率。评估了两种癫痫发作类型：主要为轻微阵挛性发作（mMS）和全身性强直阵挛性发作（GTCS）。为了研究氨己烯酸（600mg/kg，腹腔注射）的保护作用，在缺氧暴露前24小时或暴露后立即注射该药物。使用相应年龄的非缺氧动物作为对照进行比较。在非缺氧对照中，氨己烯酸给药在3天至1周的时间段内具有促惊厥作用——GTCS的发生率增加了56-57%。缺氧暴露三天后导致癫痫易感性增加，全身性强直阵挛性发作的发生率增加了60%，两种癫痫发作类型的潜伏期均短于非缺氧对照。此外，癫痫发作导致的死亡率更高（高58%）。在其他时间段，缺氧和非缺氧动物之间没有差异。在缺氧前24小时给予氨己烯酸可导致1天和3天时间段内癫痫发作导致的死亡率显著降低。缺氧暴露后立即给予氨己烯酸，在3天后评估时癫痫发作严重程度降低。我们的数据表明，低压缺氧会短暂增加癫痫易感性。缺氧暴露后给予氨己烯酸可部分消除这种作用。
