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http://dx.doi.org/10.5352/JLS.2020.30.11.939

Pretreatment with GPR88 Agonist Attenuates Postischemic Brain Injury in a Stroke Mouse Model  

Lee, Seo-Yeon (Department of Pharmacology, Wonkwang University School of Medicine)
Park, Jung Hwa (Department of Korean Medical Science, School of Korean Medicine, Pusan National University)
Kim, Min Jae (Department of Korean Medical Science, School of Korean Medicine, Pusan National University)
Choi, Byung Tae (Department of Korean Medical Science, School of Korean Medicine, Pusan National University)
Shin, Hwa Kyoung (Department of Korean Medical Science, School of Korean Medicine, Pusan National University)
Publication Information
Journal of Life Science / v.30, no.11, 2020 , pp. 939-946 More about this Journal
Abstract
Stroke is one of the leading causes of neurological disability worldwide and stroke patients exhibit a range of motor, cognitive, and psychiatric impairments. GPR88 is an orphan G protein-coupled receptor (GPCR) that is highly expressed in striatal medium spiny neurons; its deletion results in poor motor coordination and motor learning. There are currently no studies on the involvement of GPR88 in stroke or in post-stroke brain function recovery. In this study, we found a decrease in GPR88 protein and mRNA expression levels in an ischemic mouse model using Western blot and real-time PCR, respectively. In addition, we observed that, among the three types of cells derived from the brain (brain microvascular endothelial cells, BV2 microglial cells, and HT22 hippocampal neuronal cells), the expression of GPR88 was highest in HT22 neuronal cells, and that GPR88 expression was downregulated in HT22 cells under oxygen-glucose deprivation (OGD) conditions. Moreover, pretreatment with RTI- 13951-33 (10 mg/kg), a brain-penetrant GPR88 agonist, ameliorated brain injury following ischemia, as evidenced by improvements in infarct volume, vestibular-motor function, and neurological score. Collectively, our results suggest that GPR88 could be a potential drug target for the treatment of central nervous system (CNS) diseases, including ischemic stroke.
Keywords
Cerebral ischemia; GPCR; oxygen glucose deprivation; stroke;
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