title: [Therapeutic effect of anti-nucleokine monoclonal antibody on ischemic brain infarction].
abstract: Ischemic brain infarction is high among th causes of death in Japan, and the medical and social burden by severe sequela is also extremely serious. In this symposium, we show that treatment with anti-high mobility group box 1 (HMGB1) monoclonal antibody (mAb) remarkably ameliorated brain infarction induced by 2-hour occlusion of the middle cerebral artery in rats, even when the mAb was administered after the start of reperfusion. Whereas HMGB1 is usually localized in nucleus, after stimulation it is secreted into extracellular space by an unknown non-classical pathway, and exhibits an inflammatory cytokine-like activity. Treatment with mAb reduced infarct size, and the accompanying neurological deficits in locomotor function were significantly improved. In addition, some biochemical markers such as permeability of the blood-brain barrier, the expression of tumor necrosis factor-alfa, inducible nitric oxide synthase and matrix metalloproteinase-9 were altered by mAb injection. These findings indicate the usefulness of HMGB1 as a novel therapeutic to target ischemic stroke.
authors.affiliation: School of Pharmacy, Shujitsu University, 1-6-1 Nishigawara, Okayama 703-8516, Japan. morimori@shujitsu.ac.jp
authors.forename: Shuji
authors.initials: S
authors.lastname: Mori
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.forename: Hideo K
authors.initials: HK
authors.lastname: Takahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000378:metabolism; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology*; D024243:HMGB1 Protein / Q000276:immunology* / Q000502:physiology; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D024243:HMGB1 Protein; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D020780:Matrix Metalloproteinase 9