HMGB1 Neutralization Attenuates Hippocampal Neuronal Death and Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion via Suppressing Inflammatory Responses and Oxidative Stress

Neuroscience
Yue HeiWeiping Liu

Abstract

High-mobility group box-1 (HMGB1) acts as a proinflammatory molecule once released into the extracellular space and inhibition of HMGB1 signaling has been reported be neuroprotective in neurodegenerative diseases. Besides, chronic cerebral hypoperfusion (CCH) causes cognitive impairment in neurodegenerative diseases. Here we tested the protective role of HMGB1 inhibition using anti-HMGB1 neutralizing antibody (Ab) against CCH in rats after bilateral common carotid artery occlusion (2VO). 169 male Sprague-Dawley rats underwent 2VO or sham operation. PBS, anti-HMGB1 Ab (1 mg/kg), or control IgG Ab (1 mg/kg) was intravenously administered post-operation. HMGB1 translocation, blood-brain barrier (BBB) permeability and glial activation were evaluated at 3 d, as well as the levels of inflammatory cytokines and oxidative stress. NeuN immunostaining and Morris Water Maze (MWM) were performed at 3 d, 4 w and 12 w. We found that anti-HMGB1 neutralizing Ab inhibited HMGB1 translocation in hippocampal CA1 subarea and improved hippocampal HMGB1 level. Besides, anti-HMGB1 Ab preserved BBB integrity and reduced glial activation, in association with the related changes in oxidative stress (increased activities of superoxide dismutase (SOD) and...Continue Reading

Citations

Apr 5, 2020·International Journal of Molecular Sciences·Amelia Nur VidyantiChaur-Jong Hu
Dec 28, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Junliang QianJi-Tian Xu
Jun 24, 2019·European Journal of Pharmacology·Yam Nath PaudelMohd Farooq Shaikh
Jan 24, 2020·ACS Chemical Neuroscience·Yam Nath PaudelMohd Farooq Shaikh
Jul 31, 2020·Current Drug Targets·Shu WangTianfu Li

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier & Cytokines

Some cytokines are able to cross the blood brain barrier through transport systems and enter the cerebrospinal fluid and interstitial fluid spaces. Here is the latest research on cytokines crossing the blood brain barrier and how this can affect tissues within the CNS.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.