Kelly Kevin M, Jukkola Peter I, Yin Guo, Miller Eric R, Kharlamov Elena A, Shiau Deng-Shan, Strong Roger, Aronowski Jaroslaw
Department of Neurology and Allegheny Health Network Research Institute, Allegheny General Hospital, Pittsburgh, PA, USA; Departments of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA; Departments of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
Department of Neurology and Allegheny Health Network Research Institute, Allegheny General Hospital, Pittsburgh, PA, USA.
Epilepsy Res. 2018 Mar;141:38-47. doi: 10.1016/j.eplepsyres.2018.02.002. Epub 2018 Feb 10.
The mechanisms of injured brain that establish poststroke seizures and epilepsy are not well understood, largely because animal modeling has had limited development. The main objective of this study was to determine whether an arterial occlusion model of cortical stroke in young adult and aged rats was capable of generating either focal or generalized epileptic seizures within 2 months of lesioning. Four- and 20-month-old male Fischer 344 (F344) sham-operated controls and those lesioned by transient (3 h) unilateral middle cerebral artery (MCA) and common carotid artery (CCA) occlusion (MCA/CCAo) were studied by video-EEG recordings up to 2 months post-procedure. The main findings were: 1) seizures (grade 3 and above) were recorded within 2 months in both young (4-month; 0.23/h) and aged (20-month; 1.93/h) MCA/CCAo rat groups; both MCA/CCAo rat groups had more seizures recorded than the respective control groups, i.e., no seizures in young controls and 0.52/h in old controls; 2) both age and infarction independently had effects on seizure frequency; however, there was no demonstrated interaction between the two factors; and 3) there was no difference in infarct volumes comparing 4- to 20-month-old MCA/CCAo animals. In addition, all lesioned and sham-operated animals demonstrated intermittent solitary myoclonic convulsions arising out of sleep. Morbidity and mortality of animals limited the extent to which the animals could be evaluated, especially 20-month-old animals. These results suggest that transient unilateral MCA/CCAo can result in poststroke epileptic seizures in both young adult and aged F344 rats within a relatively brief period of time following lesioning.
导致中风后癫痫发作和癫痫的脑损伤机制尚未完全明确,这主要是因为动物模型的发展有限。本研究的主要目的是确定在年轻成年大鼠和老年大鼠中,皮质中风的动脉闭塞模型是否能够在损伤后2个月内引发局灶性或全身性癫痫发作。通过视频脑电图记录,对4个月和20个月大的雄性Fischer 344(F344)假手术对照组以及通过短暂(3小时)单侧大脑中动脉(MCA)和颈总动脉(CCA)闭塞(MCA/CCAo)造成损伤的大鼠进行了长达术后2个月的研究。主要发现如下:1)在年轻(4个月;0.23次/小时)和老年(20个月;1.93次/小时)MCA/CCAo大鼠组中,均在2个月内记录到癫痫发作(3级及以上);两个MCA/CCAo大鼠组记录到的癫痫发作均多于各自的对照组,即年轻对照组无癫痫发作,老年对照组为0.52次/小时;2)年龄和梗死均独立影响癫痫发作频率;然而,这两个因素之间未显示出相互作用;3)比较4个月至20个月大的MCA/CCAo动物,梗死体积无差异。此外,所有损伤和假手术动物在睡眠中均出现间歇性孤立性肌阵挛性抽搐。动物的发病率和死亡率限制了对动物的评估程度,尤其是20个月大的动物。这些结果表明,短暂性单侧MCA/CCAo可在年轻成年和老年F344大鼠损伤后的相对短时间内导致中风后癫痫发作。