title: Chronic caffeine exposure attenuates blast-induced memory deficit in mice.
abstract: OBJECTIVE
  To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms.
  
  
  METHODS
  Adult male C57BL/6 mice were used and randomly divided into five groups: control: without blast exposure, con-water: administrated with water continuously before and after blast-induced traumatic brain injury (bTBI), con-caffeine: administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine: chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine: chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR.
  
  
  RESULTS
  All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption.
  
  
  CONCLUSIONS
  Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.
authors.affiliation: Molecular Biology Center, State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery and Daping Hospital,Third Military Medical University, Chongqing, China.
authors.forename: Ya-Lei
authors.initials: YL
authors.lastname: Ning
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Xing
authors.initials: X
authors.lastname: Chen
authors.forename: Zi-Ai
authors.initials: ZA
authors.lastname: Zhao
authors.forename: Xiu-Zhu
authors.initials: XZ
authors.lastname: Zhang
authors.forename: Xing-Yun
authors.initials: XY
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yuan-Guo
authors.initials: YG
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000150:complications*; D000070642:Brain Injuries, Traumatic / Q000150:complications*; D002110:Caffeine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D043682:Receptor, Adenosine A1 / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D002110:Caffeine