Department of Neurology, University of Virginia, Charlottesville, VA, USA.
UVA Brain Institute, University of Virginia, Charlottesville, VA, USA.
Epilepsia. 2020 Dec;61(12):2811-2824. doi: 10.1111/epi.16715. Epub 2020 Oct 16.
To characterize neocortical onset status epilepticus (SE) in the C57BL/6J mouse.
We induced SE by administering homocysteine 16-18 hours after cobalt (Co) implantation. SE was monitored by video and electroencephalography (EEG). We evaluated brain structure with magnetic resonance imaging (MRI). Neurodegeneration was evaluated 72 hours after SE using Fluoro-Jade C staining.
Cobalt triggered seizures in a dose-dependent manner (median effective dose, ED = 0.78 mg) and the latency to peak seizure frequency shortened with increased dose. Animals developed SE after homocysteine administration. SE began with early intermittent focal seizures, consisting of frontal onset rhythmic spike-wave discharges manifested as focal dystonia with clonus. These focal seizures then evolved into generalized continuous convulsive activity. Behavioral manifestations of SE included tonic stiffening, bilateral limb clonus, and bilateral tonic-clonic movements, which were accompanied by generalized rhythmic spike-wave discharges on EEG. After prolonged seizures, animals became comatose with intermittent bilateral myoclonic seizures or jerks. During this period, EEG showed seizures interspersed with generalized periodic discharges on a suppressed background. MRI obtained when animals were in a coma revealed edema, midline shift in frontal lobe around the Co implantation site, and ventricular effacement. Fluoro-Jade C staining revealed neurodegeneration in the cortex, amygdala, and thalamus.
We have developed a mouse model of severe, refractory cortical-onset SE, consisting of convulsions merging into a coma, EEG patterns of cortical seizures, and injury, with evidence of widespread neocortical edema and damage. This model replicates many features of acute seizures and SE resulting from traumatic brain injury, subarachnoid, and lobar hemorrhage.
描述 C57BL/6J 小鼠新皮层起始癫痫持续状态（SE）的特征。
我们在钴（Co）植入后 16-18 小时给予同型半胱氨酸以诱导 SE。通过视频和脑电图（EEG）监测 SE。我们使用磁共振成像（MRI）评估脑结构。使用 Fluoro-Jade C 染色在 SE 后 72 小时评估神经退行性变。
钴以剂量依赖性方式引发癫痫发作（中效剂量 ED 为 0.78mg），随着剂量增加，达到峰值的潜伏期缩短。动物在给予同型半胱氨酸后发生 SE。SE 始于早期间歇性局灶性发作，包括额叶起始的节律性棘波放电，表现为局灶性张力障碍伴阵挛。这些局灶性发作随后发展为全身性连续惊厥活动。SE 的行为表现包括强直僵硬、双侧肢体阵挛和双侧强直-阵挛运动，伴有 EEG 上的全身性节律性棘波放电。在长时间发作后，动物陷入昏迷，出现间歇性双侧肌阵挛发作或抽搐。在此期间，EEG 显示发作间歇伴有抑制背景下的全身性周期性放电。当动物处于昏迷状态时进行 MRI 检查显示，Co 植入部位周围额叶中线移位、脑水肿和脑室消失。Fluoro-Jade C 染色显示皮质、杏仁核和丘脑的神经退行性变。
我们已经开发出一种严重的、难治性皮质起源 SE 小鼠模型，包括惊厥合并昏迷、皮质发作的 EEG 模式以及损伤，伴有广泛的新皮质水肿和损伤。该模型复制了外伤性脑损伤、蛛网膜下腔和脑叶出血引起的急性发作和 SE 的许多特征。
