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

Neural Regeneration Research 2023年第8期18卷 1763-1769页

作者： Li-Xiang Yang Yuan-Yuan Yao Jiu-Rong Yang Hui-Lin Cheng Xin-Jian Zhu Zhi-Jun Zhang Department of Neurosurgery Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina Department of Pharmacology Medical School of Southeast UniversityNanjingJiangsu ProvinceChina Department of Neurology Zhongda HospitalSchool of MedicineInstitution of NeuropsychiatryKey Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjingJiangsu ProvinceChina Department of Mental Health and Public Health Faculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

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.

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

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