title: Anti-high mobility group box-1 (HMGB1) antibody attenuates delayed cerebral vasospasm and brain injury after subarachnoid hemorrhage in rats.
abstract: Although delayed cerebral vasospasm (DCV) following subarachnoid hemorrhage (SAH) is closely related to the progression of brain damage, little is known about the molecular mechanism underlying its development. High mobility group box-1 (HMGB1) plays an important role as an initial inflammatory mediator in SAH. In this study, an SAH rat model was employed to evaluate the effects of anti-HMGB1 monoclonal antibody (mAb) on DCV after SAH. A vasoconstriction of the basilar artery (BA) associated with a reduction of nuclear HMGB1 and its translocation in vascular smooth muscle cells were observed in SAH rats, and anti-HMGB1 mAb administration significantly suppressed these effects. Up-regulations of inflammation-related molecules and vasoconstriction-mediating receptors in the BA of SAH rats were inhibited by anti-HMGB1 mAb treatment. Anti-HMGB1 mAb attenuated the enhanced vasocontractile response to thrombin of the isolated BA from SAH rats and prevented activation of cerebrocortical microglia. Moreover, locomotor activity and weight loss recovery were also enhanced by anti-HMGB1 mAb administration. The vasocontractile response of the BA under SAH may be induced by events that are downstream of responses to HMGB1-induced inflammation and inhibited by anti-HMGB1 mAb. Anti-HMGB1 mAb treatment may provide a novel therapeutic strategy for DCV and early brain injury after SAH.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.|Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Haruma
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Teshigawara
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tomohito
authors.initials: T
authors.lastname: Hishikawa
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Dengli
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Wake
authors.affiliation: School of Pharmacy, Shujitsu University, Okayama, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Pharmacology, Kinki University, Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: Hideo Kohka
authors.initials: HK
authors.lastname: Takahashi
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugiu
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Date
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D024243:HMGB1 Protein