• Wei Li, Shuangshuang Dai, Jianhong An, Renping Xiong, Ping Li, Xingyun Chen, Yan Zhao, Ping Liu, Hua Wang, Peifang Zhu, Jiangfan Chen, and Yuanguo Zhou.
• The Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China.
• Exp. Neurol. 2009 Jan 1; 215 (1): 69-76.

AbstractThe inactivation of the A(2A) receptor (A(2A)R) has been shown to neuroprotect against brain injury in several animal models of neurological disorders including stroke and Parkinson's disease. However, despite marked elevation of adenosine level, the role of the A(2A) in traumatic brain injury (TBI) remains unclear. In the present study, we investigated the effects of genetic inactivation of A(2A)Rs in the acute stage. The A(2A)R knock-out (KO) mice and their wild-type (WT) littermates were subjected to cortical impact injury by a dropping weight. The control group was only craniotomized without TBI. At 24 h post-TBI, the neurological deficit scores of the KO mice were significantly lower than that of WT littermates. Consistent with the behavioral changes, the brain water contents as well as histological changes and the TUNEL-positive cells of the injured cortex of the KO mice were significantly lower than that of WT littermates. Furthermore, the glutamate level in the cerebral spinal fluid (CSF) of the KO mice was also significantly lower than that of WT littermates. In addition, we found that at 12 h post-TBI the mRNA and protein levels of TNF-alpha and IL-1beta were higher in the KO mice than that in the WT littermates. However, at 24 h post-TBI, the level of TNF-alpha and IL-1beta continually increased in the WT mice but largely declined in the KO mice. These results suggest that the genetic inactivation of A(2A)R protects against TBI, which is mainly associated with the suppression of glutamate level.

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