Cognitive Impairment and Mossy Fiber Sprouting in a Rat Model of Drug-resistant Epilepsy Induced by Lithium-pilocarpine
Cognitive Impairment and Mossy Fiber Sprouting in a Rat Model of Drug-resistant Epilepsy Induced by Lithium-pilocarpine
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锂毛果芸香碱诱导的耐药性癫痫大鼠模型中的认知障碍和苔藓纤维发芽
DOI：
10.2174/1567202618666210917155408
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Guofeng Wu
中科院分区：
文献类型：
--
作者：
Jing Wu;Likun Wang;Yuanxin Huang;Qian Wu;Xingmei Luo;Yinghui Li;Siying Ren;Guofeng Wu
摘要：背景：齿状回苔藓纤维发芽（MFS）是癫痫的一种常见病理改变。以前的研究表明，它与耐药性癫痫有关，苔藓细胞控制自发性癫痫发作和空间记忆。研究方法：我们研究了锂-匹罗卡品诱导的大鼠癫痫模型中认知障碍、MFS、发作频率和耐药性之间的相关性。用苯妥英钠和苯巴比妥进行耐药筛选。采用新物体识别（NOR）实验、Morris水迷宫（MWM）实验和Timm染色检测大鼠认知功能和MFS。结果如下：结果表明，癫痫大鼠的物体记忆和空间记忆功能均明显受损，耐药癫痫大鼠仅空间记忆受损较重。耐药大鼠的自发性癫痫发作频率更高，MFS更明显。癫痫大鼠的发作频率与MWM表现显著相关，但与NOR表现无关。MFS程度与发作频率和空间记忆功能显著相关。结论：综合考虑，耐药、发作频率、空间记忆障碍和MFS之间的这些相关性提示了共同病理机制的可能性。这些相关性背后的潜在机制以及MFS在癫痫中的详细作用还需要更多的研究来阐明，苔藓细胞改变的机制可能是治疗癫痫患者癫痫发作、耐药性和认知功能障碍的重要靶点。
Abstract: Background: The mossy fiber sprouting (MFS) in the dentate gyrus is a common pathological change of epilepsy. Previous studies suggested that it is associated with drug-resistant epilepsy, and mossy cells control spontaneous seizures and spatial memory. Methods: We investigated the correlations among cognitive impairment, MFS, seizure frequency and drug resistance in a rat model of epilepsy induced by lithium–pilocarpine. Phenytoin and phenobarbital were used to screen drug resistance. Cognitive function and MFS were detected through the novel object recognition (NOR) test, Morris water maze (MWM) test and Timm staining. Results: The results showed that object memory and spatial memory functions were both significantly impaired in rats with epilepsy, and only spatial memory impairment was more severe in rats with drug-resistant epilepsy. More frequent spontaneous seizures and more obvious MFS were observed in the drug-resistant rats. The seizure frequency was significantly associated with the MWM performance but not with the NOR performance in rats with epilepsy. The degree of MFS was significantly associated with seizure frequency and spatial memory function. Conclusion: Taken together, these correlations among drug resistance, seizure frequency, spatial memory impairment and MFS suggested the possibility of a common pathological mechanism..More studies are needed to clarify the underlying mechanism behind these correlations and the detailed role of MFS in epilepsy.The mechanism of mossy cell change may be an important target for the treatment of seizures,drug resistance and cognitive dysfunction in patients with epilepsy.