Elevated HMGB-1 levels stimulate glutamate release and mediate neurotoxicity.7 Neuronal cells release HMGB-1 during seizures, accompanied by increased TLR4 expression.105 Guo and colleagues (2019), observed increased HMGB-1 and TLR4 protein expression levels and exacerbated neuronal apoptosis in KKAy mice subjected to intermittent hypoxia to induce diabetic neuropathy. Here, HMGB1 is linked to diabetic neuropathy.