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The Role of Decreased Levels of Neuronal Autophagy in Increased Susceptibility to Post-traumatic Epilepsy
Neurochemical Research ( IF 4.4 ) Pub Date : 2022-11-16 , DOI: 10.1007/s11064-022-03814-7
Jie Wang 1 , Xiaoyang Chai 2 , Fang Zhang 1 , Yuchen Li 1 , Huijun Shen 1 , Keyi Lu 3
Affiliation  

Post-traumatic epilepsy (PTE) caused by mild TBI (mild traumatic brain injury, mTBI) has a high incidence and poor prognosis, but its mechanisms are unclear. Herein, we investigated the role of reduced levels of neuronal autophagy during the latency period in the increased susceptibility to PTE. In the study, a gentle whole-body mechanical trauma rat model was prepared using Noble-Collip drums, and the extent of injury was observed by cranial CT and HE staining of hippocampal tissue. The incidence of epilepsy and its seizure form were observed 7–90 days after mTBI, and electroencephalography (EEG) was recorded during seizures in rats. Subcortical injection of non-epileptogenic dose of ferrous chloride (FeCl2) was used to observe the changes of PTE incidence after mTBI. Western blot and Real-time PCR were used to detect the level of autophagy in hippocampal cells at different time points during the latency period of PTE, and its incidence was observed after up-regulation of autophagy after administration of autophagy agonist—rapamycin. The results showed that mTBI was prepared by Noble-Collip drum, which could better simulate the clinical mTBI process. There was no intracerebral hemorrhage and necrosis in rats, no early-onset seizures, and the incidence of PTE after mTBI was 26.7%. The incidence of PTE was 56.7% in rats injected cortically with FeCl2 at a dose lower than the epileptogenic dose 48 h after mTBI, and the difference was significant compared with no FeCl2 injection, suggesting an increased susceptibility to PTE after mTBI. Further study of neuronal autophagy during PTE latency revealed that autophagy levels were reduced, and the incidence of PTE was significantly reduced after administration of rapamycin to upregulate autophagy. Taken together, the decreased level of neuronal autophagy during the latency period may be a possible mechanism for the increased susceptibility to PTE after mTBI.



中文翻译:

神经元自噬水平降低在创伤后癫痫易感性增加中的作用

轻度TBI(mild traumatic brain injury,mTBI)引起的创伤后癫痫(PTE)发病率高,预后差,但其机制尚不清楚。在此,我们研究了潜伏期神经元自噬水平降低在 PTE 易感性增加中的作用。本次研究采用 Noble-Collip 转鼓制备轻度全身机械创伤大鼠模型,通过头颅 CT 和海马组织 HE 染色观察损伤程度。在 mTBI 后 7-90 天观察癫痫的发生率及其发作形式,并记录大鼠癫痫发作期间的脑电图 (EEG)。皮质下注射非致癫痫剂量的氯化亚铁(FeCl 2)用于观察mTBI后PTE发生率的变化。采用Western blot和Real-time PCR检测PTE潜伏期不同时间点海马细胞自噬水平,观察其在给予自噬激动剂雷帕霉素上调自噬后的发生率。结果表明,mTBI采用Noble-Collip转鼓制备,能够更好地模拟临床mTBI过程。大鼠无脑出血坏死,无早发性癫痫发作,mTBI后PTE发生率为26.7%。mTBI后48 h皮层注射低于致痫剂量FeCl 2的大鼠PTE发生率为56.7% ,与不注射FeCl 2相比差异显着注射,表明 mTBI 后对 PTE 的易感性增加。对 PTE 潜伏期神经元自噬的进一步研究表明,自噬水平降低,雷帕霉素上调自噬后 PTE 的发生率显着降低。总之,潜伏期神经元自噬水平降低可能是 mTBI 后对 PTE 易感性增加的可能机制。

更新日期:2022-11-17
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