Adenosine A2A receptor deficiency exacerbates white matter lesions and cognitive deficits induced by chronic cerebral hypoperfusion in mice.
Adenosine A2A receptor inactivation consistently protects against acute ischemic brain injury; however, the role of the A2A receptor in chronic cerebral ischemia is unknown. To elucidate that, chronic cerebral hypoperfusion model was established by permanent stenosis of bilateral common carotid artery in A2A receptor knock-out mice and their wild-type littermates in this study. White matter lesions were observed after stenosis of common carotid arteries in both A2A receptor knock-out mice and wild-type mice. The demyelination-related damage and proliferation of astrocytes and microglia in white matter was observed more seriously in A2A receptor knock-out mice compared with that in wild-type mice. Working memory was also more seriously impaired in A2A receptor knock-out mice relative to wild-type mice. The mRNA expression and protein level of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) increased more remarkably in the corpus callosum in the A2A receptor knock-out mice. In conclusion, inactivation of the A2A receptor exacerbates the white matter lesions and cognitive deficits induced by chronic cerebral hypoperfusion, and this effect may be associated with increased expression of the proinflammatory cytokines in the white matter.
Duan
Wei
W
Department of Neurology, Xinqiao Hospital, Third Military Medical University, 2-V Xinqiao Street, Chongqing 400037, PR China.
Gui
Li
L
Zhou
Zhujuan
Z
Liu
Yong
Y
Tian
Hong
H
Chen
Jiang-Fan
JF
Zheng
Jian
J
D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000473:pathology / Q000503:physiopathology; D016893:Carotid Stenosis / Q000473:pathology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000473:pathology / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D003711:Demyelinating Diseases / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000473:pathology / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000172:deficiency* / Q000235:genetics
D016207:Cytokines; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A