Ictal activation of oxygen-conserving reflexes as a mechanism for sudden death in epilepsy.
Ictal activation of oxygen-conserving reflexes as a mechanism for sudden death in epilepsy.
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持续反射的发射激活是癫痫猝死的机制。
作者：
验证癫痫发作时保存氧反射（OCRs）的激活可诱导癫痫大鼠发生与人类癫痫猝死（SUDEP）相似的生理性死亡。将乌拉坦麻醉的雌性Long-Evans大鼠植入用于心电图（ECG）、皮质电图（ECoG）和呼吸热电偶的电极;静脉和动脉插管;以及喉镜引导器和插管或鼻插管，分别用于激活喉化学反射（LCR）或哺乳动物潜水反射（MDR）。红藻氨酸注射，无论是全身或腹侧海马，诱导长期急性癫痫发作。癫痫发作期间的反射激发导致20只大鼠中的18只突然死亡-所有MDR大鼠（10只）和除两只以外的所有LCR大鼠（8只）未能从OCRs的发作激活中恢复，并在反射发生后几分钟内死亡。相比之下，4/4只对照组（即，非癫痫）大鼠从64次诱导的潜水反射中恢复（每只大鼠16次），4/4只对照组从64次诱导的化学反射中恢复（每只大鼠16次）。多项测量结果与人类SUDEP报告一致。在所有病例中，终末中枢性呼吸暂停先于终末心搏停止。在OCR诱导的猝死期间，发生了与人类SUDEP相似的心率和呼吸频率波动，平均动脉压（MAP）可预测死亡，在以脑死亡时间为中心的20 s窗口中显示出17或15 mm Hg的下降（MDR和LCR分别）。OCR激活在非癫痫大鼠中从未致命。这些结果提出了一种在两种癫痫发作模型中诱导猝死的方法，所述癫痫发作模型显示与在SUDEP的人类病例中观察到的病理生理学一致。这一拟议的机制直接告知了我们小组和该领域其他人先前的发现;为研究猝死提供了一个可重复的、可诱导的动物模型;并为人类SUDEP病例中的观察结果提供了一个潜在的解释。
To test the hypothesis that death with physiological parallels to human cases of sudden unexpected death in epilepsy (SUDEP) can be induced in seizing rats by ictal activation of oxygen-conserving reflexes (OCRs). Urethane-anesthetized female Long-Evans rats were implanted with electrodes for electrocardiography (ECG), electrocorticography (ECoG), and respiratory thermocouple; venous and arterial cannulas; and a laryngoscope guide and cannula or nasal cannula for activation of the laryngeal chemoreflex (LCR) or mammalian diving reflex (MDR), respectively. Kainic acid injection, either systemic or into the ventral hippocampus, induced prolonged acute seizures. Reflex challenges during seizures caused sudden death in 18 of 20 rats—all MDR rats (10) and all but two LCR rats (8) failed to recover from ictal activation of OCRs and died within minutes of the reflexes. By comparison, 4 of 4 control (ie, nonseizing) rats recovered from 64 induced diving reflexes (16 per rat), and 4 of 4 controls recovered from 64 induced chemoreflexes (16 per rat). Multiple measures were consistent with reports of human SUDEP. Terminal central apnea preceded terminal asystole in all cases. Heart and respiratory rate fluctuations that paralleled those seen in human SUDEP occurred during OCR-induced sudden death, and mean arterial pressure (MAP) was predictive of death, showing a 17 or 15 mm Hg drop (MDR and LCR, respectively) in the 20 s window centered on the time of brain death. OCR activation was never fatal in nonseizing rats. These results present a method of inducing sudden death in two seizure models that show pathophysiology consistent with that observed in human cases of SUDEP. This proposed mechanism directly informs previous findings by our group and others in the field; provides a repeatable, inducible animal model for the study of sudden death; and offers a potential explanation for observations made in cases of human SUDEP.
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影响因子：
2.2
作者：
Budde RB;Arafat MA;Pederson DJ;Lovick TA;Jefferys JGR;Irazoqui PP
通讯作者：
Irazoqui PP
影响因子：
5.6
作者：
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影响因子：
5.5
作者：
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通讯作者：
Richerson, George B.
影响因子：
15.9
作者：
Kim, YuJaung;Bravo, Eduardo;Richerson, George B.
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Richerson, George B.
影响因子：
3.6
作者：
Berg, Anne
通讯作者：
Berg, Anne