Liu Z, Holmes G L
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, USA.
Neuroscience. 1997 Feb;76(4):1129-38. doi: 10.1016/s0306-4522(96)00412-5.
Basic fibroblast growth factor has been reported to protect neurons of various structures from excitotoxic damage. To study the effects of basic fibroblast growth factor on seizure-induced brain damage we infused the growth factor into the lateral ventricles of 35-day-old rats receiving convulsant dosages of kainic acid. Artificial cerebrospinal fluid or basic fibroblast growth factor at dosages of 0.5 ng/h or 2.5 ng/h was infused into the lateral ventricle continuously for seven days starting two days before and continuing for five days after the animals had kainic acid-induced status epilepticus. At age 80 days the animals underwent behavioural testing using the water maze, open field, and handling tests and at age 95 days were tested for seizure threshold using flurothyl inhalation. Neither artificial cerebrospinal fluid or basic fibroblast growth factor modified the latency or duration of the acute seizures following kainic acid. However, rats infused with 2.5 ng/h, but not 0.5 ng/h of basic fibroblast growth factor, had fewer spontaneous recurrent seizures, a higher seizure threshold, better performance in the handling, open field and water maze test, and less cell loss in the hippocampus when compared to rats receiving artificial cerebrospinal fluid or 0.5 ng/h of basic fibroblast growth factor. These results show that basic fibroblast growth factor has a dose-related neuroprotective effect against seizure-induced long-term behavioural deficits when administered by osmotic pump prior to seizure onset. This neuroprotective effect is not related to an anticonvulsant effect.
据报道，碱性成纤维细胞生长因子可保护各种结构的神经元免受兴奋性毒性损伤。为研究碱性成纤维细胞生长因子对癫痫诱导的脑损伤的影响，我们将该生长因子注入接受惊厥剂量 kainic 酸的 35 日龄大鼠的侧脑室。从动物发生 kainic 酸诱导的癫痫持续状态前两天开始，连续七天向侧脑室内注入人工脑脊液或剂量为 0.5 ng/h 或 2.5 ng/h 的碱性成纤维细胞生长因子，并在之后持续五天。在 80 日龄时，使用水迷宫、旷场和处理测试对动物进行行为测试，在 95 日龄时，使用氟烷吸入测试癫痫阈值。人工脑脊液或碱性成纤维细胞生长因子均未改变 kainic 酸后急性癫痫发作的潜伏期或持续时间。然而，与接受人工脑脊液或 0.5 ng/h 碱性成纤维细胞生长因子的大鼠相比，注入 2.5 ng/h（而非 0.5 ng/h）碱性成纤维细胞生长因子的大鼠自发性反复癫痫发作较少、癫痫阈值较高、在处理、旷场和水迷宫测试中表现更好，海马体中的细胞损失也较少。这些结果表明，在癫痫发作前通过渗透泵给药时，碱性成纤维细胞生长因子对癫痫诱导的长期行为缺陷具有剂量相关的神经保护作用。这种神经保护作用与抗惊厥作用无关。
