Adenosine A2A receptors in both bone marrow cells and non-bone marrow cells contribute to traumatic brain injury.

J. Neurochem. (2010) 113, 1536–1544. Adenosine A2A receptors (A_2ARs) in bone marrow-derived cells (BMDCs) are involved in regulation of inflammation and outcome in several CNS injuries; however their relative contribution to traumatic brain injury (TBI) is unknown. In this study, we created a mouse cortical impact model, and BMDC A_2ARs were selectively inactivated in wild-type (WT) mice or reconstituted in global A_2AR knockout (KO) mice (i.e. inactivation of non-BMDC A_2ARs) by bone marrow transplantation. When compared with WT mice, selective inactivation of BMDC A_2ARs significantly attenuated the neurological deficits, brain water content and cell apoptosis at 24 h post-TBI as global A_2AR KO did. However, compared with the A_2AR KO mice, selective reconstitution of BMDC A_2ARs failed to reinstate brain injury, indicating the contribution of the non-BMDC A_2AR to TBI. Furthermore, the protective outcome by selective inactivation of BMDC A_2AR or broad inactivation of non-BMDC A_2ARs was accompanied with reduced CSF glutamate level and suppression of the inflammatory cytokines interleukin-1, or interleukin-1 and tumor necrosis factor-α. These findings demonstrate that inactivation of A_2ARs in either BMDCs or non-BMDCs is sufficient to confer the protective effect as global A_2AR KO against TBI, indicating the A_2AR involvement in TBI by multiple cellular mechanisms of A_2AR involvement including inhibition of glutamate release and inflammatory cytokine expressions. [ABSTRACT FROM AUTHOR]