Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, China.
Department of Neurology, Tacheng District People's Hospital, Tacheng, 834700, Xinjiang, China.
BMC Neurol. 2022 Jan 3;22(1):3. doi: 10.1186/s12883-021-02516-x.
A decrease in hippocampal neurogenesis is considered an important cause of cognitive impairment, while changes in mossy fiber sprouting are closely related to development of spontaneous recurrent seizures in chronic temporal lobe epilepsy (TLE). Racemic l-3-n-butylphthalide (DL-NBP) can alleviate cognitive impairment in ischemic stroke and Alzheimer's disease by promoting neurogenesis. DL-NBP treatment can also improve cognitive function and reduce seizure incidence in chronic epileptic mice. However, the mechanisms of action of DL-NBP remain unclear. The aim of the present study was to examine the effects of DL-NBP on mossy fiber sprouting, hippocampal neurogenesis, spontaneous epileptic seizures, and cognitive functioning in the chronic phase of TLE.
Nissl staining was used to evaluate hippocampal injury, while immunofluorescent staining was used to analyze hippocampal neurogenesis. The duration of spontaneous seizures was measured by electroencephalography. The Morris water maze was used to evaluate cognitive function. Timm staining was used to assess mossy fiber sprouting.
TLE animals showed reduced proliferation of newborn neurons, cognitive dysfunction, and spontaneous seizures. Treatment with DL-NBP after TLE increased the proliferation and survival of newborn neurons in the dentate gyrus, reversed the neural loss in the hippocampus, alleviated cognitive impairments, and decreased mossy fiber sprouting and long-term spontaneous seizure activity.
We provided pathophysiological and morphological evidence that DL-NBP might be a useful therapeutic for the treatment of TLE.
海马神经发生减少被认为是认知障碍的一个重要原因，而苔藓纤维发芽的变化与慢性颞叶癫痫（TLE）中自发性复发性癫痫的发展密切相关。消旋 l-3-正丁基苯酞（DL-NBP）通过促进神经发生，可减轻缺血性中风和阿尔茨海默病的认知障碍。DL-NBP 治疗还可以改善慢性癫痫小鼠的认知功能并降低癫痫发作的发生率。然而，DL-NBP 的作用机制仍不清楚。本研究旨在研究 DL-NBP 对 TLE 慢性期苔藓纤维发芽、海马神经发生、自发性癫痫发作和认知功能的影响。
使用尼氏染色评估海马损伤，免疫荧光染色分析海马神经发生。通过脑电图测量自发性癫痫发作的持续时间。通过 Morris 水迷宫评估认知功能。Timm 染色评估苔藓纤维发芽。
TLE 动物表现出新生神经元增殖减少、认知功能障碍和自发性癫痫发作。TLE 后用 DL-NBP 治疗可增加齿状回新生神经元的增殖和存活，逆转海马神经元丢失，改善认知障碍，并减少苔藓纤维发芽和长期自发性癫痫活动。
我们提供了病理生理学和形态学证据，表明 DL-NBP 可能是治疗 TLE 的一种有用的治疗方法。
