Brain Alkalosis Causes Birth Asphyxia Seizures, Suggesting Therapeutic Strategy
Brain Alkalosis Causes Birth Asphyxia Seizures, Suggesting Therapeutic Strategy
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DOI：
10.1002/ana.22223
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发表时间：
2011-03-01
影响因子：
11.2
通讯作者：
Kaila, Kai
中科院分区：
文献类型：
--
作者：
Helmy, Mohamed M.;Tolner, Else A.;Kaila, Kai
目的：新生儿窒息导致癫痫发作的机制尚不清楚。为了研究脑pH变化的可能作用，我们使用了一种模拟分娩期间和产后全身CO2和O2水平变化的啮齿动物模型。方法：新生大鼠暴露于高碳酸血症(吸入气体中的20%二氧化碳)、低氧(9%O2)或两者兼有(窒息条件)1h。采用10%和5%的二氧化碳浓度分级恢复正常碳酸血症。癫痫发作的特征是行为特征和利用颅内脑电图。用皮质内微电极测量脑pH和氧，用临床仪器测量血pH、离子钙、二氧化碳、氧和乳酸。在常氧和常压恢复后的2小时内，评估暴露后脑pH的变化对癫痫负荷的影响。结果：高碳酸血症或低氧本身并不会导致暴露后明显的癫痫发作负担，但从窒息状态中恢复后伴随着较大的癫痫发作负担，这与脑组织pH值的升高密切相关，但对脑氧合作用没有影响。通过分级恢复窒息后的正常碳酸血症，可明显抑制脑内pH碱移和癫痫发作负荷。预先应用N-甲基-异丁基氨基咪胺可有效地阻止癫痫发作。解释：我们的数据表明，出生窒息恢复后的脑碱中毒在癫痫的触发中起着关键作用。我们对目前在窒息后即刻快速恢复正常碳酸血症的做法提出质疑，并提出了一种基于分级恢复正常碳酸血症的新治疗策略。Ann Neurol 2011；69：493-500
Objective: The mechanisms whereby birth asphyxia leads to generation of seizures remain unidentified. To study the possible role of brain pH changes, we used a rodent model that mimics the alterations in systemic CO2 and O-2 levels during and after intrapartum birth asphyxia.Methods: Neonatal rat pups were exposed for 1 hour to hypercapnia (20% CO2 in the inhaled gas), hypoxia (9% O2), or both (asphyxic conditions). CO2 levels of 10% and 5% were used for graded restoration of normocapnia. Seizures were characterized behaviorally and utilizing intracranial electroencephalography. Brain pH and oxygen were measured with intracortical microelectrodes, and blood pH, ionized calcium, carbon dioxide, oxygen, and lactate with a clinical device. The impact of the postexposure changes in brain pH on seizure burden was assessed during 2 hours after restoration of normoxia and normocapnia. N-methyl-isobutyl-amiloride, an inhibitor of Na+/H+ exchange, was given intraperitoneally.Results: Whereas hypercapnia or hypoxia alone did not result in an appreciable postexposure seizure burden, recovery from asphyxic conditions was followed by a large seizure burden that was tightly paralleled by a rise in brain pH, but no change in brain oxygenation. By graded restoration of normocapnia after asphyxia, the alkaline shift in brain pH and the seizure burden were strongly suppressed. The seizures were virtually blocked by preapplication of N-methyl-isobutyl-amiloride.Interpretation: Our data indicate that brain alkalosis after recovery from birth asphyxia plays a key role in the triggering of seizures. We question the current practice of rapid restoration of normocapnia in the immediate postasphyxic period, and suggest a novel therapeutic strategy based on graded restoration of normocapnia. ANN NEUROL 2011;69:493-500