Holmes G L, Chronopoulos A, Stafstrom C E, Mikati M A, Thurber S J, Hyde P A, Thompson J L
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, MA 02115.
Brain Res Dev Brain Res. 1993 May 21;73(1):71-7. doi: 10.1016/0165-3806(93)90047-e.
To determine the long-term effects of seizures on the developing brain we kindled 20-, 40-, and 60-day-old rats to stage 5 seizures and then elicited an additional 15 seizures using the same kindling stimulation. At age 80 days, all animals that reached stage 5 kindling, and their respective age-matched controls, underwent behavioral testing using the Morris water maze, open field test, and handling test. Prior to euthanasia the animals had seizure threshold tested using flurothyl inhalation. No differences were noted in time to platform in the water maze or activity level in the open field test between the kindled rats and controls in any of the three age groups. Rats kindled at age 20 and 40 were more emotional than the controls in the handling test. In the flurothyl inhalation test, rats kindled at 40 and 60 days of age had a shorter latency to all seizures stages than the controls. These results demonstrate that while kindling results in no alteration of learning, memory, or activity level, it does result in altered emotionality and activity level in immature animals, as well as reduced seizure threshold in pubescent and mature rats. The animal model used appears to be an important variable in determining the long-term effects of seizures.
为了确定癫痫发作对发育中大脑的长期影响，我们将20日龄、40日龄和60日龄的大鼠点燃至5期癫痫发作，然后使用相同的点燃刺激诱发另外15次癫痫发作。在80日龄时，所有达到5期点燃的动物及其各自年龄匹配的对照组，使用莫里斯水迷宫、旷场试验和处理试验进行行为测试。在安乐死之前，使用三氟乙烷吸入法测试动物的癫痫发作阈值。在三个年龄组中的任何一组中，点燃大鼠和对照组在水迷宫中到达平台的时间或旷场试验中的活动水平均未发现差异。在处理试验中，20日龄和40日龄点燃的大鼠比对照组更情绪化。在三氟乙烷吸入试验中，40日龄和60日龄点燃的大鼠在所有癫痫发作阶段的潜伏期均比对照组短。这些结果表明，虽然点燃不会改变学习、记忆或活动水平，但它确实会导致未成熟动物的情绪和活动水平发生改变，以及青春期和成年大鼠的癫痫发作阈值降低。所使用的动物模型似乎是确定癫痫发作长期影响的一个重要变量。
