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Adenosine A2A receptors in both bone marrow cells and non‐bone marrow cells contribute to traumatic brain injury
Author(s) -
Dai ShuangShuang,
Li Wei,
An JianHong,
Wang Hao,
Yang Nan,
Chen XingYun,
Zhao Yan,
Li Ping,
Liu Ping,
Chen JiangFan,
Zhou YuanGuo
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06716.x
Subject(s) - inflammation , tumor necrosis factor alpha , bone marrow , receptor , cytokine , traumatic brain injury , apoptosis , glutamate receptor , immunology , biology , medicine , microbiology and biotechnology , biochemistry , psychiatry
J. Neurochem. (2010) 113 , 1536–1544. Abstract Adenosine A2A receptors (A 2A Rs) 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 2A Rs were selectively inactivated in wild‐type (WT) mice or reconstituted in global A 2A R knockout (KO) mice (i.e. inactivation of non‐BMDC A 2A Rs) by bone marrow transplantation. When compared with WT mice, selective inactivation of BMDC A 2A Rs significantly attenuated the neurological deficits, brain water content and cell apoptosis at 24 h post‐TBI as global A 2A R KO did. However, compared with the A 2A R KO mice, selective reconstitution of BMDC A 2A Rs failed to reinstate brain injury, indicating the contribution of the non‐BMDC A 2A R to TBI. Furthermore, the protective outcome by selective inactivation of BMDC A 2A R or broad inactivation of non‐BMDC A 2A Rs 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 2A Rs in either BMDCs or non‐BMDCs is sufficient to confer the protective effect as global A 2A R KO against TBI, indicating the A 2A R involvement in TBI by multiple cellular mechanisms of A 2A R involvement including inhibition of glutamate release and inflammatory cytokine expressions.