Mikati M A, Holmes G L, Chronopoulos A, Hyde P, Thurber S, Gatt A, Liu Z, Werner S, Stafstrom C E
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, MA.
Ann Neurol. 1994 Sep;36(3):425-33. doi: 10.1002/ana.410360314.
To investigate the potential role of drug therapy in preventing or exacerbating seizure-related brain injury in the prepubescent brain, we administered kainic acid to rats at postnatal day 35. Therapy with daily phenobarbital was started directly before or 1 day after kainic acid was administered, and was continued through postnatal day 153. Rats receiving phenobarbital had therapeutic concentrations during most of the 24-hour dosing period, but also experienced supratherapeutic peak concentrations. The animals were subsequently tested using the water maze (a measure of visuospatial memory), open field (a measure of activity level), and handling tests (a measure of emotionality). The frequency of spontaneous recurrent seizures was monitored during and after phenobarbital therapy. Kainic acid resulted in status epilepticus on postnatal day 35 in all the rats that received it but those receiving phenobarbital first manifested a shorter and less severe status epilepticus as compared to the rats given kainic acid alone. Rats starting phenobarbital immediately before kainic acid was administered did not differ from control rats on behavioral testing and had no subsequent spontaneous recurrent seizures and no histological lesions. Rats receiving kainic acid alone performed significantly poorer than did control rats in the water maze, were more aggressive, had histological lesions, and manifested spontaneous recurrent seizures. As compared to the group treated only with kainic acid, rats receiving kainic acid followed by phenobarbital at postnatal days 36 to 153 manifested similar aggressiveness and histological lesions, similar frequency of spontaneous recurrent seizures after phenobarbital taper, and even greater disturbances in memory, learning, and activity level.(ABSTRACT TRUNCATED AT 250 WORDS)
为了研究药物治疗在预防或加剧青春期前大脑癫痫相关脑损伤中的潜在作用，我们在出生后第35天给大鼠注射了海藻酸。在注射海藻酸之前或之后1天开始每日给予苯巴比妥治疗，并持续至出生后第153天。接受苯巴比妥治疗的大鼠在24小时给药期的大部分时间内都有治疗浓度，但也出现了超治疗峰值浓度。随后使用水迷宫（视觉空间记忆的一种测量方法）、旷场试验（活动水平的一种测量方法）和处理试验（情绪的一种测量方法）对动物进行测试。在苯巴比妥治疗期间及之后监测自发性复发性癫痫的频率。海藻酸导致所有接受该药物的大鼠在出生后第35天出现癫痫持续状态，但与仅给予海藻酸的大鼠相比，接受苯巴比妥治疗的大鼠首次出现的癫痫持续状态时间更短且严重程度更低。在注射海藻酸之前立即开始使用苯巴比妥的大鼠在行为测试中与对照大鼠没有差异，并且随后没有自发性复发性癫痫发作，也没有组织学损伤。仅接受海藻酸治疗的大鼠在水迷宫中的表现明显比对照大鼠差，更具攻击性，有组织学损伤，并表现出自发性复发性癫痫发作。与仅用海藻酸治疗的组相比，在出生后第36至153天接受海藻酸后再接受苯巴比妥治疗的大鼠表现出相似的攻击性和组织学损伤，在苯巴比妥逐渐减量后自发性复发性癫痫发作的频率相似，并且在记忆、学习和活动水平方面的干扰甚至更大。（摘要截短至250字）
