Acute Non-Convulsive Status Epilepticus after Experimental Traumatic Brain Injury in Rats
Acute Non-Convulsive Status Epilepticus after Experimental Traumatic Brain Injury in Rats
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DOI：
10.1089/neu.2018.6107
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发表时间：
2019-06-01
影响因子：
4.2
通讯作者：
Pitkanen, Asia
中科院分区：
文献类型：
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作者：
Andrade, Pedro;Banuelos-Cabrera, Ivette;Pitkanen, Asia
严重创伤性脑损伤（TBI）在20-30%的患者急性期诱发癫痫发作或癫痫持续状态（SE）。我们假设外侧液体撞击损伤（FPI）引起的严重TBI触发撞击后SE。用异氟醚麻醉成年雄性sd大鼠，随机分为假手术实验对照组和外侧fpi诱导的重度TBI组。在撞击或假手术后立即植入电极，然后开始视频脑电图监测。此外，还记录了幼稚大鼠的视频脑电图。在tbi后的最初72小时内，受伤大鼠的癫痫发作与其他非惊厥性SE的典型癫痫样脑电图模式混合在一起，包括枕部间歇性节律性三角洲活动、侧化或广泛性周期性放电、尖峰-波复合体、多尖峰、多尖峰-波复合体、广泛性连续尖峰、爆发抑制或抑制。几乎所有（98%）的电图癫痫发作发生在脑外伤后0-72小时（23.2 +/- 17.4次/只）。从撞击到第一次电图发作的平均潜伏期为18.4±15.1小时，平均癫痫发作持续时间为86±57秒。高分辨率视频分析表明，只有41%的电图发作与典型的轻微行为异常相关（拉辛量表1-2）。59%的电痉挛患者没有表现出任何行为表现。在大多数大鼠中，癫痫样脑电图模式在TBI后5-6天开始自发衰减。有趣的是，也有少数假手术大鼠和幼稚大鼠出现术后癫痫发作，这与TBI大鼠非惊厥性SE的典型脑电图背景模式无关。总之，我们的数据表明，外侧fpi诱发的TBI导致非惊厥性SE，伴有细微的行为表现；这就解释了为什么直到现在才被诊断出来。外侧FPI模型为评估急性症状性非惊厥性SE的机制以及在临床相关背景下测试预防损伤后SE的治疗方法提供了一个新的平台。
Severe traumatic brain injury (TBI) induces seizures or status epilepticus (SE) in 20-30% of patients during the acute phase. We hypothesized that severe TBI induced with lateral fluid-percussion injury (FPI) triggers post-impact SE. Adult Sprague-Dawley male rats were anesthetized with isoflurane and randomized into the sham-operated experimental control or lateral FPI-induced severe TBI groups. Electrodes were implanted right after impact or sham-operation, then video-electroencephalogram (EEG) monitoring was started. In addition, video-EEG was recorded from naive rats. During the first 72 h post-TBI, injured rats had seizures that were intermingled with other epileptiform EEG patterns typical to non-convulsive SE, including occipital intermittent rhythmic delta activity, lateralized or generalized periodic discharges, spike-and-wave complexes, poly-spikes, poly-spike-and-wave complexes, generalized continuous spiking, burst suppression, or suppression. Almost all (98%) of the electrographic seizures were recorded during 0-72 h post-TBI (23.2 +/- 17.4 seizures/rat). Mean latency from the impact to the first electrographic seizure was 18.4 +/- 15.1 h. Mean seizure duration was 86 +/- 57 sec. Analysis of high-resolution videos indicated that only 41% of electrographic seizures associated with behavioral abnormalities, which were typically subtle (Racine scale 1-2). Fifty-nine percent of electrographic seizures did not show any behavioral manifestations. In most of the rats, epileptiform EEG patterns began to decay spontaneously on Days 5-6 after TBI. Interestingly, also a few sham-operated and naive rats had post-operation seizures, which were not associated with EEG background patterns typical to non-convulsive SE seen in TBI rats. To summarize, our data show that lateral FPI-induced TBI results in non-convulsive SE with subtle behavioral manifestations; this explains why it has remained undiagnosed until now. The lateral FPI model provides a novel platform for assessing the mechanisms of acute symptomatic non-convulsive SE and for testing treatments to prevent post-injury SE in a clinically relevant context.