Sarkisian M R, Rattan S, D'Mello S R, LoTurco J J
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269, USA.
Epilepsia. 1999 Apr;40(4):394-400. doi: 10.1111/j.1528-1157.1999.tb00732.x.
Disorders in normal central nervous system (CNS) development are often associated with epilepsy. This report characterizes seizures in a novel genetic model of developmental epilepsy, the Flathead (FH) rat.
Animals (n = 76) ages P0-22 were monitored for clinical and electrographic seizure activity. The effects of various AEDs on seizure frequency and duration also were assessed: phenobarbital (PB; 40 mg/kg), valproate (VPA; 400 mg/kg), or ethosuximide (ESM; 600 mg/kg).
FHs display episodes of behavior characterized by whole-body tremor, strub tail, alternating forelimb clonus, and complete tonus. EEG recordings from neocortex reveal that FH seizures are bilateral and begin around P7. Seizures occur at a frequency of approximately six per hour from P7 to P18 and the average duration of seizures increases through development. PB, VPA, and ESM failed to prevent seizures; however, PB significantly increased the interval of seizures but had no effects on the duration of seizures, whereas VPA decreased the duration of seizures and not the interval.
Seizures in FH rats occur at a constant and high frequency through a defined period in early postnatal development, and these seizures are not completely blocked by high doses of PB, VPA, or ESM. Because FH is a single-locus mutant displaying a highly regular pattern of seizure activity, it is an ideal model for examining the process of epileptogenesis in the developing brain, evaluating new AED therapies, and determining the identity of a gene essential to the normal development of cortical excitability.
正常中枢神经系统（CNS）发育紊乱常与癫痫相关。本报告描述了一种发育性癫痫的新型遗传模型——平头（FH）大鼠的癫痫发作情况。
对出生后0至22天的动物（n = 76）进行临床和脑电图癫痫活动监测。还评估了各种抗癫痫药物（AEDs）对癫痫发作频率和持续时间的影响：苯巴比妥（PB；40 mg/kg）、丙戊酸盐（VPA；400 mg/kg）或乙琥胺（ESM；600 mg/kg）。
FH大鼠表现出以全身震颤、尾巴僵硬、前肢交替阵挛和完全强直为特征的行为发作。新皮层的脑电图记录显示，FH癫痫发作是双侧性的，始于出生后第7天左右。从出生后第7天到第18天，癫痫发作频率约为每小时6次，且癫痫发作的平均持续时间随着发育而增加。PB、VPA和ESM未能预防癫痫发作；然而，PB显著增加了癫痫发作的间隔时间，但对癫痫发作的持续时间没有影响，而VPA缩短了癫痫发作的持续时间，而非间隔时间。
FH大鼠在出生后早期发育的特定时期以恒定且高频率发作癫痫，且这些癫痫发作不能被高剂量的PB、VPA或ESM完全阻断。由于FH是一个单基因座突变体，表现出高度规律的癫痫活动模式，它是研究发育中大脑癫痫发生过程、评估新的抗癫痫药物治疗以及确定对皮质兴奋性正常发育至关重要的基因身份的理想模型。
