Role of Elevated Thrombospondin-1 in Kainic Acid-Induced Status Epilepticus  

作　　者：Yurong Zhang Mengdi Zhang Wei Zhu Xiaohong Pan Qiaoyun Wang Xue Gao Chaoyun Wang Xiuli Zhang Yuxia Liu Shucui Li Hongliu Sun 

机构地区：[1]School of Pharmaceutical Sciences,Binzhou Medical University,Yantai 264003,China [2]Shandong Academy of Medical Sciences,Jinan 250062,China

出　　处：《Neuroscience Bulletin》2020年第3期263-276,共14页神经科学通报（英文版）

基　　金：the National Natural Science Foundation of China(81573412);the Key Research and Development Plan(2018GSF121004);the Natural Science Foundation of Shandong Province,China(ZR2014JL055).

摘　　要：Previous studies have suggested that thrombospondin-1(TSP-1) regulates the transforming growth factor beta 1(TGF-b1)/phosphorylated Smad2/3(p Smad2/3) pathway. Moreover, TSP-1 is closely associated with epilepsy. However, the role of the TSP-1-regulated TGFb1/p Smad2/3 pathway in seizures remains unclear. In this study, changes in this pathway were assessed following kainic acid(KA)-induced status epilepticus(SE) in rats.The results showed that increases in the TSP-1/TGF-b1/p Smad2/3 levels spatially and temporally matched the increases in glial fibrillary acidic protein(GFAP)/chondroitin sulfate(CS56) levels following KA administration.Inhibition of TSP-1 expression by small interfering RNA or inhibition of TGF-b1 activation with a Leu-Ser-Lys-Leu peptide significantly reduced the severity of KA-induced acute seizures. These anti-seizure effects were accompanied by decreased GFAP/CS56 expression and Smad2/3 phosphorylation. Moreover, inhibiting Smad2/3 phosphorylation with ponatinib or SIS3 also significantly reduced seizure severity, alongside reducing GFAP/CS56 immunoreactivity. These results suggest that the TSP-1-regulated TGF-b1/p Smad2/3 pathway plays a key role in KA-induced SE and astrogliosis, and that inhibiting this pathway may be a potential anti-seizure strategy.

关 键 词：ASTROGLIOSIS STATUS epilepticus PONATINIB Thrombospondin-1 

分 类 号：R742.1[医药卫生—神经病学与精神病学]