Sphingosine 1-phosphate receptor 1 regulates bloodbrain barrier permeability in epileptic mice

作     者：Li-Xiang Yang Yuan-Yuan Yao Jiu-Rong Yang Hui-Lin Cheng Xin-Jian Zhu Zhi-Jun Zhang Li-Xiang Yang;Yuan-Yuan Yao;Jiu-Rong Yang;Hui-Lin Cheng;Xin-Jian Zhu;Zhi-Jun Zhang

作者机构：Department of NeurosurgeryZhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina Department of PharmacologyMedical School of Southeast UniversityNanjingJiangsu ProvinceChina Department of NeurologyZhongda HospitalSchool of MedicineInstitution of NeuropsychiatryKey Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjingJiangsu ProvinceChina Department of Mental Health and Public HealthFaculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2023年第18卷第8期

页      面：1763-1769页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,Nos.82071393(to HLC),81830040(to ZJZ),82130042(to ZJZ) Science and Technology Program of Guangdong Province,No.2018B030334001(to ZJZ) the Program of Excellent Talents in Medical Science of Jiangsu Province,No.JCRCA2016006(to ZJZ) 

主　　题：adeno-associated virus astrocytes blood-brain barrier epilepsy epilepsy-associated depression-like behavior neuroinflammation pentylenetetrazol pilocarpine tight junction 

摘      要：Destruction of the blood-brain barrier is a critical component of epilepsy *** studies have demonstrated that sphingosine 1-phosphate receptor 1 contributes to the modulation of vascular ***,its effect on blood-brain barrier permeability in epileptic mice remains *** this study,we prepared pilocarpine-induced status epilepticus models and pentylenetetrazol-induced epilepsy models in C57BL/6 mice.S1P1 expression was increased in the hippocampus after status epilepticus,whereas tight junction protein expression was decreased in epileptic mice compared with *** injection of SEW2871,a specific agonist of sphingosine-1-phosphate receptor 1,decreased the level of tight junction protein in the hippocampus of epileptic mice,increased blood-brain barrier leakage,and aggravated the severity of seizures compared with the control.W146,a specific antagonist of sphingosine-1-phosphate receptor 1,increased the level of tight junction protein,attenuated blood-brain barrier disruption,and reduced seizure severity compared with the ***,sphingosine 1-phosphate receptor 1 promoted the generation of interleukin-1βand tumor necrosis factor-αand caused *** of tight junction protein and blood-brain barrier integrity by sphingosine 1-phosphate receptor 1 was reversed by minocycline,a neuroinflammation *** tests revealed that sphingosine 1-phosphate receptor 1 exacerbated epilepsy-associated depression-like ***,specific knockdown of astrocytic S1P1 inhibited neuroinflammatory responses and attenuated blood-brain barrier leakage,seizure severity,and epilepsy-associated depression-like *** together,our results suggest that astrocytic sphingosine 1-phosphate receptor 1 exacerbates blood-brain barrier disruption in the epileptic brain by promoting neuroinflammation.