title: Role of HMGB1 translocation to neuronal nucleus in rat model with 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.
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041,China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041,China. Electronic address: hxlixihong@126.com.
authors.forename: Xihong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041,China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041,China.
authors.forename: Jichong
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041,China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041,China.
authors.forename: Fengyan
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041,China.
authors.forename: Shiping
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu 610041, China; Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041,China. Electronic address: mudz@scu.edu.cn.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024243:HMGB1 Protein / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D011773:Pyruvates / Q000494:pharmacology; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D018805:Sepsis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: C000593874:Ager protein, rat; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D018696:Neuroprotective Agents; D011773:Pyruvates; D000067759:Receptor for Advanced Glycation End Products; D051996:Transcription Factor RelA; C046522:ethyl pyruvate
keywords: Brain injury; HMGB1; Sepsis