Anti-high mobility group box-1 (HMGB1) antibody inhibits hemorrhage-induced brain injury and improved neurological deficits in rats.

Abstract

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.

• Authors: Dengli Wang, Keyue Liu, Hidenori Wake, Kiyoshi Teshigawara, Shuji Mori, Masahiro Nishibori
• Journal: Scientific reports (Sci Rep) Vol. 7 Pg. 46243 (04 10 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 28393932 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Aquaporin 4
• HMGB1 Protein
• Interleukin-1beta

Topics

• Animals
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Aquaporin 4 (metabolism)
• Astrocytes (drug effects, metabolism)
• Blood-Brain Barrier (drug effects, metabolism, pathology)
• Brain Edema (blood, complications, drug therapy, pathology)
• Brain Injuries (blood, drug therapy, etiology)
• Cerebral Hemorrhage (blood, complications)
• HMGB1 Protein (antagonists & inhibitors, blood)
• Inflammation (blood, metabolism, pathology)
• Interleukin-1beta (metabolism)
• Male
• Microglia (drug effects, metabolism)
• Motor Activity (drug effects)
• Neurons (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Permeability (drug effects)
• Rats, Wistar
• Vasoconstriction