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.
| Original language | English |
|---|---|
| Pages (from-to) | 25-31 |
| Number of pages | 7 |
| Journal | Yakugaku Zasshi |
| Volume | 129 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2009 |
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Keywords
- Antibody therapeutics
- Ischemic brain infarction
- Target therapy
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
Cite this
Therapeutic effect of anti-nucleokine monoclonal antibody on ischemic brain infarction. / Mori, Shuji; Liu, Keyue; Takahashi, Hideo K.; Nishibori, Masahiro.
In: Yakugaku Zasshi, Vol. 129, No. 1, 01.2009, p. 25-31.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Therapeutic effect of anti-nucleokine monoclonal antibody on ischemic brain infarction
AU - Mori, Shuji
AU - Liu, Keyue
AU - Takahashi, Hideo K.
AU - Nishibori, Masahiro
PY - 2009/1
Y1 - 2009/1
N2 - 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.
AB - 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.
KW - Antibody therapeutics
KW - Ischemic brain infarction
KW - Target therapy
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U2 - 10.1248/yakushi.129.25
DO - 10.1248/yakushi.129.25
M3 - Article
VL - 129
SP - 25
EP - 31
JO - Yakugaku Zasshi
JF - Yakugaku Zasshi
SN - 0031-6903
IS - 1
ER -