H., Aucott J., Lundberg H., Salo L., Klevenvall P., Damberg L., Ottosson U., Andersson S., Holmin H., Erlandsson Harris Supplementary Material for: Neuroinflammation in Response to Intracerebral Injections of Different HMGB1 Redox Isoforms <b><i>Background:</i></b> Neuroinflammation triggered by infection or trauma is the cause of central nervous system dysfunction. High-mobility group box 1 protein (HMGB1), released from stressed and dying brain cells, is a potent neuroinflammatory mediator. The proinflammatory functions of HMGB1 are tightly regulated by post-translational redox modifications, and we here investigated detailed neuroinflammatory responses induced by the individual redox isoforms. <b><i>Methods:</i></b> Male Dark Agouti rats received a stereotactic injection of saline, lipopolysaccharide, disulfide HMGB1, or fully reduced HMGB1, and were accessed for blood-brain barrier modifications using magnetic resonance imaging (MRI) and inflammatory responses by immunohistochemistry. <b><i>Results and Conclusions:</i></b> Significant blood-brain barrier disruption appeared 24 h after injection of lipopolysaccharide, disulfide HMGB1, or fully reduced HMGB1 compared to controls, as assessed in post-gadolinium T1-weighted MRI images and confirmed by increased uptake of FITC-conjugated dextran. Immunohistochemistry revealed that both HMGB1 isoforms also induced a local production of IL-1β. Additionally, disulfide HMGB1 increased major histocompatibility complex class II expression and apoptosis. Together, the results demonstrate that extracellular, cerebral HMGB1 causes significant blood-brain barrier disruption in a redox-independent manner and activates several components of neuroinflammation. Blocking HMGB1 might potentially improve clinical outcome in conditions such as stroke and traumatic brain injury. HMGB1;Brain;Redox;Neuroinflammation;Blood-brain barrier 2018-02-23
    https://karger.figshare.com/articles/dataset/Supplementary_Material_for_Neuroinflammation_in_Response_to_Intracerebral_Injections_of_Different_HMGB1_Redox_Isoforms/5918590
10.6084/m9.figshare.5918590.v1