title: Curcumin attenuates brain edema in mice with intracerebral hemorrhage through inhibition of AQP4 and AQP9 expression.
abstract: OBJECTIVE
  Aquaporins (AQPs) are the water-channels that play important roles in brain water homeostasis and in cerebral edema induced by brain injury. In this study we investigated the relationship between AQPs and a neuroprotective agent curcumin that was effective in the treatment of brain edema in mice with intracerebral hemorrhage (ICH).
  
  
  METHODS
  ICH was induced in mice by autologous blood infusion. The mice immediately received curcumin (75, 150, 300 mg/kg, ip). The Rotarod test scores, brain water content and brain expression of AQPs were measured post ICH. Cultured primary mouse astrocytes were used for in vitro experiments. The expression of AQP1, AQP4 and AQP9 and NF-κB p65 were detected using Western blotting or immunochemistry staining.
  
  
  RESULTS
  Curcumin administration dose-dependently reduced the cerebral edema at d 3 post ICH, and significantly attenuated the neurological deficits at d 5 post ICH. Furthermore, curcumin dose-dependently decreased the gene and protein expression of AQP4 and AQP9, but not AQP1 post ICH. Treatment of the cultured astrocytes with Fe(2+) (10-100 μmol/L) dose-dependently increased the expression and nuclear translocation of NF-κB p65 and the expression of AQP4 and AQP9, which were partly blocked by co-treatment with curcumin (20 μmol/L) or the NF-κB inhibitor PDTC (10 μmol/L).
  
  
  CONCLUSIONS
  Curcumin effectively attenuates brain edema in mice with ICH through inhibition of the NF-κB pathway and subsequently the expression of AQP4 and AQP9. Curcumin may serve as a potential therapeutic agent for ICH.
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Bao-feng
authors.initials: BF
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhen-wen
authors.initials: ZW
authors.lastname: Cui
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhi-hong
authors.initials: ZH
authors.lastname: Zhong
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yu-hao
authors.initials: YH
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Qing-fang
authors.initials: QF
authors.lastname: Sun
authors.affiliation: 1] Neuroscience and Neuroengineering Research Center, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai 200030, China [2] Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Guo-yuan
authors.initials: GY
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Liu-guan
authors.initials: LG
authors.lastname: Bian
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D051401:Aquaporin 4 / Q000032:analysis / Q000235:genetics*; D020346:Aquaporins / Q000032:analysis / Q000235:genetics*; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D003474:Curcumin / Q000627:therapeutic use*; D015536:Down-Regulation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C491638:Aqp9 protein, mouse; D051401:Aquaporin 4; D020346:Aquaporins; D016328:NF-kappa B; D003474:Curcumin