Genetic inactivation of adenosine A2A receptors attenuates acute traumatic brain injury in the mouse cortical impact model

The inactivation of the A_2A receptor (A_2AR) 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_2ARs in the acute stage. The A_2AR 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-α and IL-1β were higher in the KO mice than that in the WT littermates. However, at 24 h post-TBI, the level of TNF-α and IL-1β continually increased in the WT mice but largely declined in the KO mice. These results suggest that the genetic inactivation of A_2AR protects against TBI, which is mainly associated with the suppression of glutamate level.