Nature Medicine10, 1081 - 1087 (2004)
Published online: 26 September 2004; | doi:10.1038/nm1103
Selective inactivation or reconstitution of adenosine A2A receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury
1
Department of Neurology, Boston University School of Medicine, 715 Albany Street, C329, Boston, Massachusetts 02118, USA.
2
Neuroscience Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA.
Correspondence should be addressed to Jiang-Fan Chen chenjf@bu.edu
Inactivation of the adenosine A2A receptor (A2AR) consistently protects against ischemic brain injury and other neural insults, but the relative contribution of A2ARs on peripheral inflammatory cells versus A2ARs expressed on neurons and glia is unknown. We created a chimeric mouse model in which A2ARs on bone marrow−derived cells (BMDCs) were selectively inactivated or reconstituted by bone marrow transplantation. Selective reconstitution of A2ARs on BMDCs (A2AR knockout mice transplanted with wild-type bone marrow cells) largely reinstates ischemic brain injury in global A2AR knockout mice. Conversely, selective inactivation of A2ARs on BMDCs (wild-type mice transplanted with A2AR knockout bone marrow cells) attenuates infarct volumes and ischemia-induced expression of several proinflammatory cytokines in the brain, but exacerbates ischemic liver injury. These results indicate that the A2AR-stimulated cascade in BMDCs is an important modulator of ischemic brain injury and that ischemic brain and liver injuries are regulated distinctly by A2ARs on BMDCs.
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