Ning Ya-Lei, Yang Nan, Chen Xing, Zhao Zi-Ai, Zhang Xiu-Zhu, Chen Xing-Yun, Li Ping, Zhao Yan, Zhou Yuan-Guo
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.
Chin J Traumatol. 2015;18(4):204-11. doi: 10.1016/j.cjtee.2015.10.003.
To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms.
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.
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.
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.
研究三种不同的慢性咖啡因给药方式对爆炸所致记忆功能障碍的影响，并探讨其潜在机制。
选用成年雄性C57BL/6小鼠，随机分为五组：对照组：未遭受爆炸暴露；对照 - 水组：在爆炸诱导的创伤性脑损伤（bTBI）前后持续给予水；对照 - 咖啡因组：在bTBI前后持续给予咖啡因1个月；预咖啡因组：在bTBI前慢性给予咖啡因1个月，bTBI后停药；后咖啡因组：在bTBI后慢性给予咖啡因。遭受中等强度的爆炸损伤后，在爆炸损伤后1、4和8周使用莫里斯水迷宫（MWM）范式记录小鼠的学习和记忆表现。在bTBI后24小时、1、4和8周检查神经功能缺损评分、谷氨酸浓度、促炎细胞因子产生和神经病理变化，以评估早期和长期阶段的脑损伤。使用qPCR检测腺苷A1受体表达。
三种慢性咖啡因暴露方式均改善了爆炸所致的记忆缺陷，这与在损伤不同阶段对兴奋性毒性、炎症、星形胶质细胞增生和神经元丢失的神经保护作用相关。持续咖啡因治疗在bTBI的早期和长期阶段均发挥积极作用；bTBI前和bTBI后咖啡因治疗分别倾向于在bTBI的早期和长期阶段发挥神经保护作用。腺苷A1受体表达上调可能有助于慢性咖啡因摄入的有益作用。
由于含咖啡因的饮料在 civilian 和 military 人员中广泛消费且易于获取，该结果可能为爆炸所致神经创伤及随之而来的认知障碍提供一种有前景的预防策略。
