Role of HMGB1 translocation to neuronal nucleus in rat model with septic brain injury. (3rd April 2017)

• Record Type: Journal Article
• Authors: Li, Yafei; Li, Xihong; Qu, Yi; Huang, Jichong; Zhu, Tingting; Zhao, Fengyan; Li, Shiping; Mu, Dezhi
• Is Part Of: Neuroscience letters. Volume 645(2017)
• Page Start: 90
• Page End: 96
• Publication Date: 2017-04-03
• Subjects: HMGB1 -- Sepsis -- Brain injury; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.11.047
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: We investigated the role of HMGB1 in sepsis. Sepsis increases HMGB1 cytoplasmic translocation in neurons. HMGB1 inhibitor downregulates sepsis-induced RAGE and NF-κBp65 expression. HMGB1inhibition have therapeutic potential for septic brain injury. Abstract: High-mobility Group Box-1 (HMGB1) is a central late proinflammatory cytokine that triggers the inflammatory response during sepsis. However, whether HMGB1 is involved in the pathogenesis of septic brain damage is unknown. In this study, we investigated the role of HMGB1 in regulating brain injury in a rat model of sepsis. Wistar rats were subjected to cecal ligation and puncture (CLP) to induce septic brain injury. Hematoxylin and eosin staining was used to detect pathological changes in the cortex. The cellular localization of HMGB1 was determined using immunostaining. Cortical levels of HMGB1, its receptor for advanced glycation end-products (RAGE), and downstream effecter, nuclear factor kappa-B (NF-κB) subunit p65, were detected via western blot.HMGB1was increased in the cytoplasm via translocation from the nucleus predominantly in neurons. Moreover, RAGE and NF-κB p65 were upregulated after septic brain injury. Ethyl pyruvate, an inhibitor of HMGB1, down-regulated the expression of RAGE and NF-κB p65via inhibiting HMGB1 expression in the cytoplasm. Collectively, our findings suggest that HMGB1 and its signaling transduction have critical roles in the pathogenesis of septic brain injury. HMGB1 inhibition might be a potential new therapeutic target for septic brain injury.