Adenosine A2A Receptor Deficiency Alleviates Blast-Induced Cognitive Dysfunction
Adenosine A2A Receptor Deficiency Alleviates Blast-Induced Cognitive Dysfunction
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DOI：
10.1038/jcbfm.2013.127
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发表时间：
2013-08
影响因子：
6.3
通讯作者：
Yalei Ning;N. Yang;Xing-yun Chen;R. Xiong;Xiuyun Zhang;Ping Li;Yan Zhao;Xing-yun Chen;Ping Liu;Yan Peng;Zheng-Guo Wang;Jiang-fan Chen;Yuan-Guo Zhou
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文献类型：
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作者：
Yalei Ning;N. Yang;Xing-yun Chen;R. Xiong;Xiuyun Zhang;Ping Li;Yan Zhao;Xing-yun Chen;Ping Liu;Yan Peng;Zheng-Guo Wang;Jiang-fan Chen;Yuan-Guo Zhou
创伤性脑损伤（TBI），特别是爆炸性冲击波诱发的TBI（bTBI），已成为军事人员中最常见的损伤。认知功能的破坏是bTBI最严重的后果之一，因为其长期影响使幸存者无法履行其现役并恢复正常的平民生活。然而，其机制知之甚少，也没有可用的治疗方法。本研究探讨腺苷A2A受体（adenosine A2A receptor，A2AR）在脑外伤后认知功能障碍中的作用及其机制。在遭受中度全身冲击伤后，缺乏A2AR的小鼠（A2AR敲除（KO））表现出比野生型小鼠更轻的严重程度和更短的空间参考记忆和工作记忆受损的持续时间。此外，bTBI诱导的皮质和海马病变，以及促炎细胞因子表达，谷氨酸释放，水肿，细胞丢失，和胶质细胞增生的早期和长期阶段的损伤，在A2AR KO小鼠显着减弱。结果表明，早期损伤和慢性神经病理损害是bTBI诱导的认知功能障碍的重要机制，并通过阻止A2AR激活，损害可以减轻。这些研究结果表明，A2 AR拮抗作用是轻中度bTBI和随之而来的认知障碍的潜在治疗策略。
Traumatic brain injury (TBI), particularly explosive blast-induced TBI (bTBI), has become the most prevalent injury among military personnel. The disruption of cognitive function is one of the most serious consequences of bTBI because its long-lasting effects prevent survivors fulfilling their active duty and resuming normal civilian life. However, the mechanisms are poorly understood and there is no treatment available. This study investigated the effects of adenosine A2A receptor (A2AR) on bTBI-induced cognitive deficit, and explored the underlying mechanisms. After being subjected to moderate whole-body blast injury, mice lacking the A2AR (A2AR knockout (KO)) showed less severity and shorter duration of impaired spatial reference memory and working memory than wild-type mice did. In addition, bTBI-induced cortical and hippocampal lesions, as well as proinflammatory cytokine expression, glutamate release, edema, cell loss, and gliosis in both early and prolonged phases of the injury, were significantly attenuated in A2AR KO mice. The results suggest that early injury and chronic neuropathological damages are important mechanisms of bTBI-induced cognitive impairment, and that the impairment can be attenuated by preventing A2AR activation. These findings suggest that A2AR antagonism is a potential therapeutic strategy for mild-to-moderate bTBI and consequent cognitive impairment.