High mobility group box-1 (HMGB1) antagonist BoxA suppresses status epilepticus-induced neuroinflammatory responses associated with Toll-like receptor 2/4 down-regulation in rats.

08:00 EDT 12th April 2019 | BioPortfolio

Summary of "High mobility group box-1 (HMGB1) antagonist BoxA suppresses status epilepticus-induced neuroinflammatory responses associated with Toll-like receptor 2/4 down-regulation in rats."

It has been generally accepted that inflammatory responses induced by status epilepticus (SE) in the brain are associated with microglial activation. One important regulator of microglial activation is high mobility group box-1 (HMGB1) protein. HMGB1 exerts its influence on microglia via various pathways including Toll-like receptor (TLR) subtypes 2 and 4. To explore the HMGB1 role in the SE-induced microglial activation and the involvement of TLRs we conducted in vivo and ex vivo experiments using the HMGB1 antagonist BoxA. Blood-brain barrier (BBB) permeability, brain water content, hippocampal neuroinflammation and neuronal apoptosis were measured 24 hours after the pilocarpine induction of status epilepticus (SE) in Sprague-Dawley rats treated with BoxA. In ex vivo experiments, post-SE microglia cells were isolated from the hippocampal CA1 area and subjected to lipopolysaccharide (LPS) stimulation followed by inflammatory cytokine IL-1β and IL-6 by qPCR and HMGB1, TLR2, TLR3 by Western blotting. A significant down-regulation of IL-1β, IL-6 and TNF-α but not HMGB1 was found in BoxA-treated compared to untreated animals. These changes were associated with decreased BBB permeability, reduced hippocampal neuronal apoptosis and reduction in hippocampal microglial activation. We conclude that BoxA-induced suppression of HMGB1-mediated neuroinflammatory responses is associated with TLR-2 and 4 down-regulation and should be explored as a potential therapeutic target.


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Name: Brain research
ISSN: 1872-6240


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