The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Therapeutic effects of stiripentol against ischemia-reperfusion injury in gerbils focusing on cognitive deficit, neuronal death, astrocyte damage and blood brain barrier leakage in the hippocampus

  • Shin, Myoung Cheol (Department of Emergency Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine) ;
  • Lee, Tae-Kyeong (Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Lee, Jae-Chul (Department of Neurobiology, Kangwon National University School of Medicine) ;
  • Kim, Hyung Il (Department of Emergency Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine) ;
  • Park, Chan Woo (Department of Emergency Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine) ;
  • Cho, Jun Hwi (Department of Emergency Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine) ;
  • Kim, Dae Won (Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangnung-Wonju National University) ;
  • Ahn, Ji Hyeon (Department of Neurobiology, Kangwon National University School of Medicine) ;
  • Won, Moo-Ho (Department of Neurobiology, Kangwon National University School of Medicine) ;
  • Lee, Choong-Hyun (Department of Pharmacy, College of Pharmacy, Dankook University)
  • Received : 2021.10.25
  • Accepted : 2021.11.30
  • Published : 2022.01.01
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Abstract

Stiripentol is an anti-epileptic drug for the treating of refractory status epilepticus. It has been reported that stiripentol can attenuate seizure severity and reduce seizure-induced neuronal damage in animal models of epilepsy. The objective of the present study was to investigate effects of post-treatment with stiripentol on cognitive deficit and neuronal damage in the cornu ammonis 1 (CA1) region of the hippocampus proper following transient ischemia in the forebrain of gerbils. To evaluate ischemia-induced cognitive impairments, passive avoidance test and 8-arm radial maze test were performed. It was found that post-treatment with stiripentol at 20 mg/kg, but not 10 or 15 mg/kg, reduced ischemia-induced memory impairment. Transient ischemia-induced neuronal death in the CA1 region was also significantly attenuated only by 20 mg/kg stiripentol treatment after transient ischemia. In addition, 20 mg/kg stiripentol treatment significantly decreased ischemia-induced astrocyte damage and immunoglobulin G leakage. In brief, stiripentol treatment after transient ischemia ameliorated transient ischemia-induced cognitive impairment in gerbils, showing that pyramidal neurons were protected and astrocyte damage and blood brain barrier leakage were significantly attenuated in the hippocampus. Results of this study suggest stiripentol can be developed as a candidate of therapeutic drug for ischemic stroke.

Keywords

Acknowledgement

The authors would like to appreciate Ms. Hyun Sook Kim and Mr. Seung Uk Lee for their technical help in this study.

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