Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Canada.
Department of Physiology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania.
Elife. 2016 Nov 22;5:e19352. doi: 10.7554/eLife.19352.
Seizures are often followed by sensory, cognitive or motor impairments during the postictal phase that show striking similarity to transient hypoxic/ischemic attacks. Here we show that seizures result in a severe hypoxic attack confined to the postictal period. We measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. Using inhibitors of these targets we separated the seizure from the resulting severe hypoxia and show that structure specific postictal memory and behavioral impairments are the consequence of this severe hypoperfusion/hypoxic event. Thus, epilepsy is much more than a disease hallmarked by seizures, since the occurrence of postictal hypoperfusion/hypoxia results in a separate set of neurological consequences that are currently not being treated and are preventable.
发作后阶段常伴有感觉、认知或运动障碍，与短暂缺氧/缺血发作有明显相似性。在这里，我们发现发作会导致局限于发作后阶段的严重缺氧发作。我们在自由活动的啮齿动物的局部区域测量了脑氧合，发现发作终止后会发生严重的缺氧事件（pO < 10 mmHg）。该事件持续超过一个小时，由低灌注介导，在癫痫患者中普遍存在，并可通过抑制环氧化酶-2 或 L 型钙通道来减轻。使用这些靶点的抑制剂，我们将发作与由此产生的严重缺氧分开，并表明特定于结构的发作后记忆和行为障碍是这种严重低灌注/缺氧事件的结果。因此，癫痫不仅仅是一种以发作为特征的疾病，因为发作后低灌注/缺氧的发生会导致一系列目前未得到治疗且可预防的神经系统后果。
