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Original Article

Korean J Physiol Pharmacol 2022; 26(1): 47-57

Published online January 1, 2022 https://doi.org/10.4196/kjpp.2022.26.1.47

Copyright © Korean J Physiol Pharmacol.

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

Myoung Cheol Shin1,#, Tae-Kyeong Lee2,#, Jae-Chul Lee3, Hyung Il Kim1,4, Chan Woo Park1, Jun Hwi Cho1, Dae Won Kim5, Ji Hyeon Ahn3,6, Moo-Ho Won3,*, and Choong-Hyun Lee7,*

1Department of Emergency Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon 24289, 2Department of Biomedical Science, Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, 3Department of Neurobiology, Kangwon National University School of Medicine, Chuncheon 24341, 4Department of Emergency Medicine, Dankook University Hospital, Dankook University College of Medicine, Cheonan 31116, 5Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangnung-Wonju National University, Gangneung 25457, 6Department of Physical Therapy, College of Health Science, Youngsan University, Yangsan 50510, 7Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, Korea

Correspondence to:Moo-Ho Won
E-mail: mhwon@kangwon.ac.kr
Choong-Hyun Lee
E-mail: anaphy@dankook.ac.kr

#These authors contributed equally to this work.

Received: October 25, 2021; Revised: November 23, 2021; Accepted: November 30, 2021

This is an Open Access journal distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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: Blood-brain barrier, Brain ischemia, Hippocampus, Neuroprotection, Stiripentol