title: Hydroquinone Strongly Alleviates Focal Ischemic Brain Injury via Blockage of Blood-Brain Barrier Disruption in Rats.
abstract: Hydroquinone (HQ), a major benzene metabolite, occurs naturally in various plants and is manufactured for commercial use. Although HQ displays various biological effects, its neuroprotective effects following ischemic insults have not been investigated. In this study, we first examined neuroprotective effects of HQ in a rat model of transient focal cerebral ischemia. Animals were subjected to transient middle cerebral artery occlusion for 120 min. HQ (50 or 100 mg/kg) or vehicle was intraperitoneally administered once at 30 min after ischemia-reperfusion. Neuroprotection by treatment with 100 mg/kg of HQ was shown using evaluation of neurological deficits, positron-emission tomography (PET) and 2,3,5-triphenyltetrazoliumchloride (TTC) staining. In addition, HQ treatment significantly attenuated ischemia-induced Evans blue dye extravasation from blood vessels and significantly increased immunoreactivities of SMI-71 (an endothelial BBB marker) and glucose transporter-1 (GLUT-1, an endothelial cell marker) in ischemic cortex compared to the vehicle-treated ischemia-operated group. Confocal microscopy and western blot analysis also showed that HQ treatment maintained expressions of tight junction proteins (zonula occludens-1 and occludin) in the ischemic cortex. Post-treatment with HQ protected neurons from transient focal cerebral ischemic injury and the neuroprotective effect of HQ might be closely associated with prevention of BBB disruption via maintaining SMI-71 and GLUT-1 expressions as well as prevention of the degradation of zonula occludens-1 and occludin proteins.
authors: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea mhwon@kangwon.ac.kr.
authors: Joon
authors: J
authors: Ha Park
authors: Department of Oral Anatomy, College of Dentistry and Research institute of Oral Biology, Gangneung-Wonju National University, Gangneung 25457, South Korea mhwon@kangwon.ac.kr.
authors: Ki-Yeon
authors: KY
authors: Yoo
authors: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: In
authors: I
authors: Hye Kim
authors: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Jeong-Hwi
authors: JH
authors: Cho
authors: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Jae-Chul
authors: JC
authors: Lee
authors: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea.
authors: Ji
authors: J
authors: Hyeon Ahn
authors: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Hyun
authors: H
authors: Jin Tae
authors: Institute of Integrative Traditional and Western Medicine, Medical College Yangzhou University, Yangzhou 225001, China.
authors: Bing
authors: B
authors: Chun Yan
authors: Department of Biochemistry and Molecular Biology, and Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung 25457, South Korea.
authors: Dae
authors: D
authors: Won Kim
authors: Division of Analytical Bio-imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Kangwon 24341, South Korea.
authors: Ok
authors: O
authors: Kyu Park
authors: Division of Analytical Bio-imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Kangwon 24341, South Korea.
authors: Seung-Hae
authors: SH
authors: Kwon
authors: Division of Analytical Bio-imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, Kangwon 24341, South Korea.
authors: Song
authors: S
authors: Her
authors: Molecular Imaging Research Center, Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul 01812, South Korea.
authors: Jin
authors: J
authors: Su Kim
authors: Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Jung
authors: J
authors: Hoon Choi
authors: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 31116, South Korea.
authors: Choong
authors: C
authors: Hyun Lee
authors: Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science Seoul National University, Seoul 08826, South Korea.
authors: In
authors: I
authors: Koo Hwang
authors: Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, South Korea.
authors: Jae
authors: J
authors: Youl Cho
authors: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Jun
authors: J
authors: Hwi Cho
authors: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, South Korea.
authors: Young-Guen
authors: YG
authors: Kwon
authors: Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea.
authors: Sungwoo
authors: S
authors: Ryoo
authors: Department of Molecular and Cellular Biochemistry School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Young-Myeong
authors: YM
authors: Kim
authors: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chuncheon 24252, South Korea mhwon@kangwon.ac.kr.|Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, South Korea.
authors: Moo-Ho
authors: MH
authors: Won
authors: Department of Food Science and Nutrition, Hallym University, Chuncheon, 24252, South Korea.
authors: Il
authors: I
authors: Jun Kang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects*; D019610:Cytoprotection; D004195:Disease Models, Animal; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006873:Hydroquinones / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D062793:Occludin / Q000378:metabolism; D049268:Positron-Emission Tomography; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D006873:Hydroquinones; D018696:Neuroprotective Agents; D062793:Occludin; C568987:Ocln protein, rat; C495679:Slc2a1 protein, rat; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; C031927:hydroquinone
keywords: blood–brain barrier; experimental ischemic stroke; hydroquinone; neuroprotective effects; post-treatment; tight junction.