title: Tetrandrine ameliorates cognitive impairment via inhibiting astrocyte-derived S100B activation in a rat model of chronic cerebral hypoperfusion.
abstract: OBJECTIVE
  To investigate the effects of tetrandrine (Tet) on cognitive impairment induced by chronic cerebral hypoperfusion and its potential anti-inflammatory mechanism by modulating the expression of S100B, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS).
  
  
  METHODS
  Chronic cerebral hypoperfusion was induced by ligation of the bilateral common carotid arteries for 8 weeks. Rats were treated with Tet (10 mg/kg or 30 mg/kg) intraperitoneally every 3 days for 4 weeks. Cognitive function of rats was evaluated by the Morris water maze. Hematoxylin eosin (H & E) and Nissl staining were used to observe neuronal damage in the hippocampal CA1 region. Immunofluorescence, quantitative real-time polymerase chain reaction (QT-PCR), and western blot were performed to measure S100B, IL-1 beta, TNF-alpha, and iNOS levels in the CA1 region of chronic cerebral hypoperfusion rats.
  
  
  RESULTS
  The Tet-treated group significantly decreased the escape latency of chronic cerebral hypoperfusion rats in finding the hidden platform (P <0.05). Compared with the 2-VO (two-vessel occlusion) group, more neurons with regular morphology and/or Nissl bodies in the hippocampus were observed in the Tet-treated group, suggesting attenuated neuronal damage and degeneration. Additionally, S100B, IL-1 beta, TNF-alpha, and iNOS levels were significantly (P <0.05) decreased in the CA1 region of the chronic cerebral hypoperfusion affected rats treated with Tet.
  
  
  CONCLUSIONS
  Our results found that Tet could improve cognitive impairment in the chronic cerebral hypoperfusion rats. Tetrandrine may be a novel and promising candidate for future treatment and/or prevention of chronic cerebral hypoperfusion via inhibiting S100B activation and decreasing the expression of IL-1 beta, TNF-alpha, and iNOS in the hippocampal CA1 region.
authors.affiliation: The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Neurology, Chongqing, China.
authors.forename: Lianlian
authors.initials: L
authors.lastname: Chen
authors.forename: Lixue
authors.initials: L
authors.lastname: Chen
authors.forename: Yanling
authors.initials: Y
authors.lastname: Lv
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Cui
authors.forename: Gui
authors.initials: G
authors.lastname: Bei
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Qin
authors.forename: Jiying
authors.initials: J
authors.lastname: Zhou
authors.forename: Tan
authors.initials: T
authors.lastname: Ge
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D044182:Benzylisoquinolines / Q000494:pharmacology / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000378:metabolism*; D002908:Chronic Disease; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051381:Rats; D064568:S100 Calcium Binding Protein beta Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; D064568:S100 Calcium Binding Protein beta Subunit; C579158:S100b protein, rat; C009438:tetrandrine