Immediate post-injury HMGB1 neutralization prevents synaptic dysfunction in burn and hindlimb unloaded rats

IntroductionSevere burns are known to provoke neuroinflammation and contribute to cognitive deficits, but the mechanism of action remains poorly understood. We hypothesize that early release of extracellular high mobility group box 1 (HMGB1), a key driver for inflammation, triggers the burn−induced hyperinflammation and associated synaptic dysfunction.

Unavoidable immobilization prolongs inflammation and worsens burn outcomes. We examined the therapeutic potential of an anti−HMGB1 neutralizing antibody in improving the neurological outcomes in burned and immobilized rats.MethodsAdult male rats received >30% total body surface area (TBSA) scald burns.

After injury, animals received either no treatment, chicken anti−HMGB1, or isotype control IgY antibody (2 mg/kg, intraperitoneal or combined with subcutaneous Alzet pump delivery). Burn−injured, treated rats underwent 14 days of hindlimb unloading (HLU) in metabolic cages, followed by 7 days of mobile recovery.

Burned rats without treatment were pair−fed and housed in standard cages without suspension, as were sham−burn controls. All animals were euthanized 21 days post−injury for sample collection.