Intranasal nerve growth factor attenuating the seizure onset via p75R/Caspase pathway in the experimental epilepsy
Intranasal nerve growth factor attenuating the seizure onset via p75R/Caspase pathway in the experimental epilepsy
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鼻内神经生长因子通过 p75R/Caspase 通路减轻实验性癫痫发作
DOI：
10.1016/j.brainresbull.2017.07.006
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发表时间：
2017-09-01
影响因子：
3.8
通讯作者：
Wang, Furong
中科院分区：
文献类型：
--
作者：
Lei, Jing'an;Feng, Fang;Wang, Furong
背景：神经生长因子（Nerve growth factor，NGF）具有神经保护作用，但由于分子量大，难以通过血脑屏障。本研究采用鼻内注射神经生长因子（NGF）治疗实验性癫痫，方法：给大鼠注射戊四氮（40 mg/kg）诱发癫痫发作。根据行为学表现，将成功的模型随机分为对照组和NGF组，分别给予培养基或NGF鼻内给药。记录癫痫发作时间和持续时间。免疫组化和TUNEL染色检测神经元丢失情况。结果：鼻内注射神经生长因子可明显减少癫痫发作次数，缩短癫痫发作持续时间。鼻内注射神经生长因子可减轻癫痫脑内神经元的丢失。NGF组TUNEL阳性细胞数少于对照组（P < 0.05）。结论：鼻内注射神经生长因子可通过抑制p75 R/Caspase信号通路而保护癫痫脑神经元。鼻内注射神经生长因子可能是治疗癫痫的一种新策略。
Background: Nerve growth factor (NGF) shows neuroprotection while it is hard to cross the blood-brain barrier due to its large molecular weight. Our study used intranasal delivery of NGF to treat the experimental epilepsy.Methods: The seizure was induced by injection of pentylenetetrazol (40 mg/kg) into the rat. Based on the behavior performance, the successful models were randomized into control and NGF groups, given medium or NGF intranasally, respectively. The onset and duration of seizure were recorded. The neuron loss was assessed by immunohistochemistry and TUNEL staining. The expressions of Caspase-3, p75R and TrkA were measured by western blotting.Results: Intranasal NGF significantly reduced the seizure onset and shortened the seizure duration. Intranasal NGF alleviated the neuron loss in the epileptic brain. The number of TUNEL-positive cells in the NGF group was less than that in the control group (P < 0.05). Overexpression of Caspase-3 and activation of p75R induced by seizure were inhibited by intranasal NGF.Conclusion: Intranasal NGF protected neurons in the epileptic brain by inactivation of p75R/Caspase pathway. Intranasal NGF may be a novel therapeutic strategy for epilepsy.