HMGB1 Neutralization Attenuates Hippocampal Neuronal Death and Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion via Suppressing Inflammatory Responses and Oxidative Stress
| Autor: | Rong Chen, Dakuan Gao, Yue Hei, Qianfa Long, Xicai Yi, Weiping Liu |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Morris water navigation task chemical and pharmacologic phenomena Pharmacology Hippocampal formation medicine.disease_cause Neuroprotection Hippocampus Proinflammatory cytokine Brain Ischemia Superoxide dismutase Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Medicine Animals Cognitive Dysfunction HMGB1 Protein Inflammation Neurons biology Cell Death business.industry General Neuroscience Malondialdehyde Rats Oxidative Stress 030104 developmental biology chemistry biology.protein Female NeuN business 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Neuroscience. 383 |
| ISSN: | 1873-7544 |
| Popis: | 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 catalase (CAT), and decreased malondialdehyde (MDA) production) and inflammatory cytokines (increased gene expression of IL-1β, IL-6 and TNF) at 3 d. Additionally, anti-HMGB1 neutralizing Ab improved hippocampal CA1 neuronal survival and behavioral outcomes in the chronic phase (4 w and 12 w). Taken together, these findings suggest that HMGB1 neutralization suppresses hippocampal inflammatory responses and oxidative stress in the acute phase, and these changes exert long-lasting beneficial effects in the chronic phase of CCH. |
| Databáze: | OpenAIRE |
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