4BRAIN, Department of Neurology, Ghent University Hospital, Ghent, Belgium.
4BRAIN, Department of Neurology, Ghent University Hospital, Ghent, Belgium.
Epilepsy Res. 2020 Aug;164:106364. doi: 10.1016/j.eplepsyres.2020.106364. Epub 2020 May 21.
Intracerebral hemorrhage (ICH) is a known risk factor for the development of seizures, but little is known about the pathophysiology of seizures in the acute phase post-ICH and their influence on functional outcome. With the use of an animal model, the underlying pathophysiology could be further unraveled. The aim of our study was to optimize the rat collagenase stroke model for the detection of acute symptomatic seizures using video-EEG monitoring.
Male Sprague-Dawley rats were implanted with scalp electrodes and a craniotomy was made for later injection of collagenase. After one week of baseline video-EEG recording, rats were injected with 0.6 U collagenase in 0.7 μL saline in left striatum, in close proximity of the piriform cortex, and immediately reconnected to the video-EEG setup for 7 days. Occurrence of clinical and electrographic seizures was assessed and functional deficits were evaluated on several time points using the cylinder test, Neurological Deficit Scale (NDS) and forelimb placing test. At day 7 post-ICH, animals were euthanized. The volume and cortical involvement of the hemorrhage were assessed by histological examination of the brain tissue, using Cresyl violet stain.
Collagenase injection induced ICH in all animals with a mean volume of 27 mm³ (SEM 7 mm³, range 4-92 mm³). Functional deficits were present in all animals injected with collagenase (pre-ICH vs post-ICH, p < 0.001). Epileptic seizures occurred in 5/11 animals and started between 1 and 61 h after ICH induction. Behavioral changes were observed in 13/15 seizures.
Injecting rats with 0.6 U of collagenase is a useful model to study the occurrence of acute symptomatic seizures post-ICH as it results in ICH in all animals without mortality, 45% incidence of ICH-induced acute symptomatic seizures and measurable functional deficits.
脑出血（ICH）是癫痫发作的已知危险因素，但对 ICH 后急性期癫痫发作的病理生理学及其对功能结局的影响知之甚少。通过动物模型，可以进一步阐明潜在的病理生理学。本研究的目的是通过视频-脑电图监测优化胶原酶卒中大鼠模型，以检测急性症状性癫痫发作。
雄性 Sprague-Dawley 大鼠植入头皮电极，并进行开颅术，以便以后在左侧纹状体注射胶原酶。在基线视频-脑电图记录一周后，将 0.6 U 胶原酶在 0.7 μL 盐水中注射到靠近梨状皮质的部位，然后立即重新连接到视频-脑电图设备上进行 7 天监测。评估临床和脑电图癫痫发作的发生，并在几个时间点使用圆筒测试、神经功能缺损量表（NDS）和前肢放置测试评估功能缺陷。ICH 后第 7 天，处死动物。使用 Cresyl violet 染色对脑组织进行组织学检查，评估血肿的体积和皮质受累情况。
胶原酶注射诱导所有动物发生 ICH，平均体积为 27 mm³（SEM 7 mm³，范围 4-92 mm³）。所有注射胶原酶的动物均存在功能缺陷（ICH 前 vs ICH 后，p < 0.001）。5/11 只动物发生癫痫发作，癫痫发作始于 ICH 诱导后 1 至 61 小时。在 13/15 次癫痫发作中观察到行为改变。
向大鼠注射 0.6 U 胶原酶是研究 ICH 后急性症状性癫痫发作发生的有用模型，因为它导致所有动物发生 ICH，无死亡率，45%的 ICH 诱导的急性症状性癫痫发作发生率和可测量的功能缺陷。
