Zou Jing, Wang Xinxin, Huang Ligang, Liu Juan, Kong Yingying, Li Shengtian, Lu Qinchi
Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Key Laboratory for the Genetics of Development and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, China.
Front Neurol. 2019 Jan 31;10:37. doi: 10.3389/fneur.2019.00037. eCollection 2019.
Epilepsy is a highly disabling neurological disorder. Brain insult is the most critical cause of epilepsy in adults. This study aimed to find reliable and efficient biomarkers for predicting secondary epilepsy. The LiCl-pilocarpine (LiCl-Pilo) chronic epilepsy rat model was used, and rat cerebrospinal fluid (CSF) was collected 5 days after status epilepticus (SE). The CSF was analyzed using the label-free LC-ESI-Q-TOF-MS/MS. Differential expression of proteins was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The corresponding protein level in the CSF of patients with encephalitis in the postacute phase was determined using ELISA and compared between patients with and without symptomatic epilepsy after encephalitis during a 2-year follow-up. The proteomics and ELISA results showed that the protein level of kininogen (KNG) was obviously elevated in both CSF and hippocampus, but not in serum, 5 days after the onset of SE in LiCl-Pilo chronic epilepsy model rats. In patients with encephalitis, the protein level of KNG in the CSF in the postacute phase was significantly elevated in patients with a recurrent epileptic seizure during a 2-year follow-up than in patients without a recurrent seizure. KNG in the CSF may serve as a potential biomarker for predicting epileptogenesis in patients with encephalitis.
癫痫是一种严重致残的神经系统疾病。脑损伤是成人癫痫最关键的病因。本研究旨在寻找可靠且有效的生物标志物以预测继发性癫痫。使用氯化锂-匹罗卡品(LiCl-Pilo)慢性癫痫大鼠模型,在癫痫持续状态(SE)后5天收集大鼠脑脊液(CSF)。采用无标记液相色谱-电喷雾电离-四极杆-飞行时间串联质谱(LC-ESI-Q-TOF-MS/MS)分析脑脊液。通过酶联免疫吸附测定(ELISA)和蛋白质印迹法确认蛋白质的差异表达。采用ELISA测定脑炎后急性期患者脑脊液中的相应蛋白质水平,并在2年随访期间比较脑炎后有和无症状性癫痫患者之间的差异。蛋白质组学和ELISA结果显示,在LiCl-Pilo慢性癫痫模型大鼠中,SE发作后5天,激肽原(KNG)的蛋白质水平在脑脊液和海马中均明显升高,但在血清中未升高。在脑炎患者中,在2年随访期间,复发癫痫发作的患者急性期后脑脊液中KNG的蛋白质水平显著高于未复发癫痫发作的患者。脑脊液中的KNG可能作为预测脑炎患者癫痫发生的潜在生物标志物。