Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA.
J Neurosci. 2010 Jan 6;30(1):404-15. doi: 10.1523/JNEUROSCI.4093-09.2010.
The development of acquired epilepsy after a perinatal hypoxic-ischemic (HI) insult was investigated in rats. After unilateral carotid ligation with hypoxia on postnatal day 7, cortical electroencephalographic and behavioral seizures were recorded with continuous radio-telemetry and video. Chronic recordings were obtained between 2 and 12 months of age in freely behaving HI-treated and sham control rats. The hypotheses were that the acquired epilepsy is directly associated with an ischemic infarct (i.e., no lesion, no epilepsy), and the resultant epilepsy is temporally progressive. Every HI-treated rat with a cerebral infarct developed spontaneous epileptiform discharges and recurrent seizures (100%); in contrast, no spontaneous epileptiform discharges or seizures were detected with continuous monitoring in the HI-treated rats without infarcts. The initial seizures at 2 months generally showed focal onset and were nonconvulsive. Subsequent seizures had focal onsets that propagated to the homotopic contralateral cortex and were nonconvulsive or partial; later seizures often appeared to have bilateral onset and were convulsive. Spontaneous epileptiform discharges were initially lateralized to ipsilateral neocortex but became bilateral over time. The severity and frequency of the spontaneous behavioral and electrographic seizures progressively increased over time. In every epileptic rat, seizures occurred in distinct clusters with seizure-free periods as long as a few weeks. The progressive increase in seizure frequency over time was associated with increases in cluster frequency and seizures within each cluster. Thus, prolonged, continuous seizure monitoring directly demonstrated that the acquired epilepsy after perinatal HI was progressive with seizure clusters and was consistently associated with a cerebral infarct.
本研究旨在探讨围产期缺氧缺血(HI)损伤后获得性癫痫的发展。在新生后第 7 天进行单侧颈总动脉结扎和缺氧后,使用连续无线电遥测和视频记录皮质脑电图和行为性癫痫发作。在 HI 处理和假手术对照大鼠自由活动期间,于 2 至 12 月龄进行慢性记录。研究假设为获得性癫痫与缺血性梗死直接相关(即无病变,无癫痫),且由此产生的癫痫呈时间进展性。每只伴有脑梗死的 HI 处理大鼠均发展出自发性癫痫样放电和复发性癫痫(100%);相比之下,在没有梗死的 HI 处理大鼠中,连续监测未发现自发性癫痫样放电或癫痫。2 月龄时的初始癫痫发作通常表现为局灶性发作,且无惊厥。随后的癫痫发作起源于同侧对侧皮质,呈无惊厥或部分性发作;后期的癫痫发作通常呈双侧性发作,且呈惊厥性。自发性癫痫样放电最初偏向同侧新皮质,但随时间推移逐渐变为双侧。自发性行为和脑电图癫痫发作的严重程度和频率随时间逐渐增加。在每只癫痫大鼠中,癫痫发作以明显的发作簇出现,且发作间期长达数周。随时间推移,癫痫发作频率逐渐增加与发作簇频率和每个发作簇内的癫痫发作增加有关。因此,长时间、连续的癫痫监测直接证明,围产期 HI 后获得性癫痫呈进行性发展,具有癫痫发作簇,且始终与脑梗死有关。