Recently, activation of the
adenosine A2A receptors has been shown to exert protection against peripheral tissue
injuries but aggravation in the central nervous system (CNS)
injuries. To explore the different effects of
adenosine A2A receptors and try to perform some new treatment strategies for peripheral tissue and CNS
traumas, we constructed the mouse models of skin
trauma, skin combined radiation-impaired
wound and
traumatic brain injury (TBI), respectively. Wild type mice and A2A receptor gene knockout mice were both used in the experiments. In skin
trauma and combined radiation-impaired
wound models, the time of wound healing was observed, while in TBI model, neurological deficit scores, water content in injured brain and
glutamate concentration in cerebral spinal fluid (CSF) were detected at 24 h after TBI. The results showed that in skin
trauma and combined radiation-impaired
wound models,
CGS21680 (an agonist of the A2A receptors) promoted while A2A receptor gene knockout delayed the course of skin wound healing. On the contrary, in TBI model, A2A receptor gene knockout, not
CGS21680, showed a protective role by inhibition of
glutamate release. These data further indicate that promoting
glutamate release may account for the different effects of A2A receptor activation in CNS injury and peripheral tissue injury models. These findings may provide some experimental evidence and a new strategy for clinical treatment of peripheral tissue damages by agonists of A2A receptors, while treatment of CNS
injuries by antagonists of A2A receptors.