Adenosine A2A receptor deficiency exacerbates white matter lesions and cognitive deficits induced by chronic cerebral hypoperfusion in mice
Adenosine A2A receptor deficiency exacerbates white matter lesions and cognitive deficits induced by chronic cerebral hypoperfusion in mice
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DOI：
10.1016/j.jns.2009.05.010
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发表时间：
2009-10-15
影响因子：
4.4
通讯作者：
Zheng, Jian
中科院分区：
文献类型：
--
作者：
Duan, Wei;Gui, Li;Zheng, Jian
腺苷A（2A）受体失活一贯地保护急性缺血性脑损伤;然而，A（2A）受体在慢性脑缺血中的作用尚不清楚。为了阐明这一点，本研究通过永久性狭窄双侧颈总动脉建立了A（2A）受体基因敲除小鼠及其野生型同窝小鼠的慢性脑低灌注模型。在A（2A）受体敲除小鼠和野生型小鼠中，颈总动脉狭窄后均观察到白色病变。与野生型小鼠相比，A（2A）受体基因敲除小鼠脑白色中星形胶质细胞和小胶质细胞的脱髓鞘损伤和增殖更为严重。相对于野生型小鼠，A（2A）受体敲除小鼠的工作记忆受损也更严重。在A（2A）受体敲除小鼠的胼胝体中，促炎细胞因子包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1 β）和白细胞介素-6（IL-6）的mRNA表达和蛋白水平更显著地增加。总之，A（2A）受体的失活加重了慢性脑灌注不足引起的白色损害和认知障碍，这种作用可能与白色物质中促炎细胞因子的表达增加有关。(C)2009爱思唯尔有限公司版权所有。
Adenosine A(2A) receptor inactivation consistently protects against acute ischemic brain injury; however, the role of the A(2A) 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 A(2A) 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 A(2A) 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 A(2A) receptor knock-out mice compared with that in wild-type mice. Working memory was also more seriously impaired in A(2A) 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-1 beta (IL-1 beta), and interleukin-6 (IL-6) increased more remarkably in the corpus callosum in the A(2A) receptor knock-out mice. In conclusion, inactivation of the A(2A) 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. (C) 2009 Elsevier B.V. All rights reserved.