Low doses of the selective adenosine A2A receptor agonist CGS21680 are protective in a rat model of transient cerebral ischemia
Low doses of the selective adenosine A2A receptor agonist CGS21680 are protective in a rat model of transient cerebral ischemia
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DOI：
10.1016/j.brainres.2014.01.014
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发表时间：
2014-03-10
期刊：
影响因子：
2.9
通讯作者：
Pedata, Felicita
中科院分区：
文献类型：
--
作者：
Melani, Alessia;Corti, Francesca;Pedata, Felicita
有证据表明，腺苷A（2A）受体亚型在卒中中起着至关重要的作用。局灶性缺血后，A（2A）腺苷受体在缺血性纹状体和皮质的神经元和小胶质细胞中央区水平过表达。腺苷A（2A）受体亚型不仅定位于中枢水平，也定位于外周血，在那里它被认为具有抗炎作用。本研究旨在探讨腺苷A（2A）受体激动剂CGS21680对短暂性大脑内侧动脉闭塞（MCAo）大鼠模型的神经保护作用。脑中动脉闭塞1 h，引起短暂性脑缺血。CGS21680（0.01和0.1 mg/kg, i.p.）在缺血后4小时开始按慢性方案给药（每天2次，连用7天）。0.1 mg/kg剂量的CGS21680可瞬间增加心脏频率，但未改变血压。当剂量为0.01 mg/kg时，药物对心脏频率和血压均无影响。在短暂的MCAo后，两种剂量的CGS21680在第一天到7天内都没有神经功能障碍。此时，它减少了小胶质细胞增生、星形胶质细胞增生，改善了纹状体中的髓磷脂组织以及缺血皮质和纹状体的细胞结构。短暂MCAo 2天后，CGS21680减少了缺血组织中浸润的粒细胞数量。数据表明，系统给药CGS21680具有免疫抑制作用。(C) 2014 Elsevier B.V.版权所有
Evidence indicate that adenosine A(2A) receptor subtype is of critical importance in stroke. An overexpression of A(2A) adenosine receptors occurs at central level on neurons and microglia of ischemic striatum and cortex after focal ischemia. Adenosine A(2A) receptor subtype is localized not only at central level but also peripherally on blood cells, where it is known to exert antiinflammatory effect. Purpose of the present work was to investigate the putative neuroprotective effect of the adenosine A(2A) receptor agonist CGS21680 in a rat model of transient medial cerebral artery occlusion (MCAo). Transient cerebral ischemia was induced by 1 h occlusion of MCA. CGS21680 (0.01 and 0.1 mg/kg, i.p.) was administered starting 4 h after ischemia according to a chronic protocol (twice/day for 7 days). CGS21680, at the dose of 0.1 mg/kg transiently increased heart frequency but did not modify blood pressure. At the dose of 0.01 mg/kg the drug did not modify either heart frequency or blood pressure. Following transient MCAo, CGS21680 at both doses protected from neurological deficit from the first day up to 7 days thereafter. At this time, it has reduced microgliosis, astrogliosis and improved myelin organization in the striatum and cytoarchitecture of the ischemic cortex and striatum. Two days after transient MCAo, CGS21680 has reduced the number of infiltrated granulocytes into the ischemic tissue. Data indicate that CGS21680 systemically administered is protective by immunosuppressive effects. (C) 2014 Elsevier B.V. All rights reserved.