Takafumi Nakano1, Chisa Nishigami2, Keiichi Irie3, Yutaka Shigemori4, Kazunori Sano2, Yuta Yamashita2, Takayuki Myose2, Koji Tominaga5, Koichi Matsuo5, Yoshihiko Nakamura4, Hiroyasu Ishikura4, Hidetoshi Kamimura6, Takashi Egawa5, Kenichi Mishima2. 1. Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Jyonan, Fukuoka, Japan; Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Jyonan, Fukuoka, Japan; Department of Pharmacy, Fukuoka University Hospital, Fukuoka, Japan. 2. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Jyonan, Fukuoka, Japan. 3. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Jyonan, Fukuoka, Japan. Electronic address: kirie@cis.fukuoka-u.ac.jp. 4. Department of Emergency and Critical Care Medicine, Fukuoka University Hospital, Fukuoka, Japan. 5. Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Jyonan, Fukuoka, Japan. 6. Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Jyonan, Fukuoka, Japan; Department of Pharmacy, Fukuoka University Hospital, Fukuoka, Japan.
Abstract
BACKGROUND: Aquaporin 4 (AQP4) is a water-selective transport protein expressed in astrocytes throughout the central nervous system. AQP4 level increases after cerebral ischemia and results in ischemic brain edema. Brain edema markedly influences mortality and motor function by elevating intracranial pressure that leads to secondary brain damage. Therefore, AQP4 is an important target to improve brain edema after cerebral ischemia. The Japanese herbal Kampo medicine, goreisan, is known to inhibit AQP4 activity. Here, we investigated whether goreisan prevents induction of brain edema by cerebral ischemia via AQP4 using 4-hour middle cerebral artery occlusion (4h MCAO) mice. METHODS: Goreisan was orally administered at a dose of 500 mg/kg twice a day for 5 days before MCAO. AQP4 expression and motor coordination were measured by Western blotting and rotarod test, respectively. RESULTS: Brain water content of 4h MCAO mice was significantly increased at 24 hours after MCAO. Treatment with goreisan significantly decreased both brain water content and AQP4 expression in the ischemic brain at 24 hours after MCAO. In addition, treatment with goreisan alleviated motor coordination deficits at 24 hours after MCAO. CONCLUSIONS: The results of this study suggested that goreisan may be a useful new therapeutic option for ischemic brain edema.
BACKGROUND:Aquaporin 4 (AQP4) is a water-selective transport protein expressed in astrocytes throughout the central nervous system. AQP4 level increases after cerebral ischemia and results in ischemic brain edema. Brain edema markedly influences mortality and motor function by elevating intracranial pressure that leads to secondary brain damage. Therefore, AQP4 is an important target to improve brain edema after cerebral ischemia. The Japanese herbal Kampo medicine, goreisan, is known to inhibit AQP4 activity. Here, we investigated whether goreisan prevents induction of brain edema by cerebral ischemia via AQP4 using 4-hour middle cerebral artery occlusion (4h MCAO) mice. METHODS: Goreisan was orally administered at a dose of 500 mg/kg twice a day for 5 days before MCAO. AQP4 expression and motor coordination were measured by Western blotting and rotarod test, respectively. RESULTS: Brain water content of 4h MCAOmice was significantly increased at 24 hours after MCAO. Treatment with goreisan significantly decreased both brain water content and AQP4 expression in the ischemic brain at 24 hours after MCAO. In addition, treatment with goreisan alleviated motor coordination deficits at 24 hours after MCAO. CONCLUSIONS: The results of this study suggested that goreisan may be a useful new therapeutic option for ischemic brain edema.
Authors: Jeremy N Ford; Qihao Zhang; Elizabeth M Sweeney; Alexander E Merkler; Mony J de Leon; Ajay Gupta; Thanh D Nguyen; Jana Ivanidze Journal: Front Aging Neurosci Date: 2022-04-08 Impact factor: 5.702