1. Academic Validation
  2. Role of Elevated Thrombospondin-1 in Kainic Acid-Induced Status Epilepticus

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

  • Neurosci Bull. 2020 Mar;36(3):263-276. doi: 10.1007/s12264-019-00437-x.
Yurong Zhang 1 Mengdi Zhang 1 Wei Zhu 2 Xiaohong Pan 1 Qiaoyun Wang 1 Xue Gao 1 Chaoyun Wang 1 Xiuli Zhang 1 Yuxia Liu 1 Shucui Li 1 Hongliu Sun 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, 264003, China.
  • 2 Shandong Academy of Medical Sciences, Jinan, 250062, China.
  • 3 School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, 264003, China. sun_china6@163.com.
Abstract

Previous studies have suggested that thrombospondin-1 (TSP-1) regulates the transforming growth factor beta 1 (TGF-β1)/phosphorylated SMAD2/3 (pSmad2/3) pathway. Moreover, TSP-1 is closely associated with epilepsy. However, the role of the TSP-1-regulated TGF-β1/pSmad2/3 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-β1/pSmad2/3 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-β1 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-β1/pSmad2/3 pathway plays a key role in KA-induced SE and astrogliosis, and that inhibiting this pathway may be a potential anti-seizure strategy.

Keywords

Astrogliosis; Ponatinib; Status epilepticus; Thrombospondin-1.

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