title: Critical contribution of adenosine A2A receptors in bone marrow-derived cells to white matter lesions induced by chronic cerebral hypoperfusion.
abstract: Adenosine A2A receptors (A2ARs) in distinct cellular types may exert different and even opposite effects on many neurologic disorders; A2ARs in bone marrow-derived cells (BMDCs) have been shown to play important roles in various brain injuries. We previously showed that global A2AR inactivation aggravates chronic cerebral hypoperfusion-induced white matter lesions (WMLs); however, the specific cell populations responsible for A2AR-mediated signaling remain unknown. In the present study, we developed chimeric mice in which A2ARs were either selectively inactivated or reconstituted in BMDCs by transplanting bone marrow from global A2AR gene knockout or wild-type mice into wild-type or gene knockout mice, respectively. Chimeric mice were subsequently subjected to chronic cerebral hypoperfusion by bilateral common carotid artery stenosis, and the effects of BMDC A2ARs on WMLs were evaluated. The selective inactivation of A2AR in BMDCs aggravated chronic cerebral hypoperfusion-induced WMLs, promoted microglial activation, and increased proinflammatory cytokine expression, whereas the selective reconstitution or activation of A2AR in BMDCs using the agonist CGS21680 produced the opposite effects. These results demonstrate that A2ARs in BMDCs are important modulators of WMLs induced by chronic cerebral hypoperfusion; this modulation might be associated with the regulation of inflammatory cytokine production.
authors.affiliation: From the Department of Neurology, Xinqiao Hospital (HR, WD, ZG, XH, LJ, QH, JZ), and Department of Pathology, Southwest Hospital (SX), Third Military Medical University; and Medical Examination Center, Chinese People's Liberation Army 324 Hospital (HR), Chongqing, China; and Department of Cell and Developmental Biology, Vanderbilt University, Nashville, Tennessee (HZ).
authors.forename: Hong
authors.initials: H
authors.lastname: Ran
authors.forename: Wei
authors.initials: W
authors.lastname: Duan
authors.forename: Zili
authors.initials: Z
authors.lastname: Gong
authors.forename: Senlin
authors.initials: S
authors.lastname: Xu
authors.forename: He
authors.initials: H
authors.lastname: Zhu
authors.forename: Xianhua
authors.initials: X
authors.lastname: Hou
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Qifen
authors.initials: Q
authors.lastname: He
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002560:Cerebrovascular Circulation / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000473:pathology*; D002908:Chronic Disease; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000502:physiology*; D066127:White Matter / Q000098:blood supply / Q000473:pathology*
chemical_list: D043705:Receptor, Adenosine A2A