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Anti-high mobility group box-1 (HMGB1) antibody inhibits hemorrhage-induced brain
injury and improved neurological deficits in rats
#MMPMID28393932
Wang D
; Liu K
; Wake H
; Teshigawara K
; Mori S
; Nishibori M
Sci Rep
2017[Apr]; 7
(?): 46243
PMID28393932
show ga
As one of the most lethal stroke subtypes, intracerebral hemorrhage (ICH) is
acknowledged as a serious clinical problem lacking effective treatment. Available
evidence from preclinical and clinical studies suggests that inflammatory
mechanisms are involved in the progression of ICH-induced secondary brain injury.
High mobility group box-1 (HMGB1) is a ubiquitous and abundant nonhistone
DNA-binding protein, and is also an important proinflammatory molecule once
released into the extracellular space from the nuclei. Here, we show that
treatment with neutralizing anti-HMGB1 mAb (1?mg/kg, i.v. twice) remarkably
ameliorated ICH-injury induced by local injection of collagenase IV in the
striatum of rats. Administration of anti-HMGB1 mAb inhibited the release of HMGB1
into the extracellular space in the peri-hematomal region, reduced serum HMGB1
levels and decreased brain edema by protecting blood-brain barrier integrity, in
association with decreased activated microglia and the expression of
inflammation-related factors at 24?h after ICH. Consequently, anti-HMGB1 mAb
reduced the oxidative stress and improved the behavioral performance of rats.
These results strongly indicate that HMGB1 plays a critical role in the
development of ICH-induced secondary injury through the amplification of plural
inflammatory responses. Intravenous injection of neutralizing anti-HMGB1 mAb has
potential as a novel therapeutic strategy for ICH.
|Animals
[MESH]
|Antibodies, Monoclonal/pharmacology/*therapeutic use
[MESH]
free
free
free
