Protective Effect of Adenosine A(2B) Receptor Agonist, BAY60-6583, Against Transient Focal Brain Ischemia in Rat.
Protective Effect of Adenosine A(2B) Receptor Agonist, BAY60-6583, Against Transient Focal Brain Ischemia in Rat.
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DOI：
10.3389/fphar.2020.588757
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发表时间：
2020
影响因子：
5.6
通讯作者：
Pedata F
中科院分区：
文献类型：
--
作者：
Dettori I;Gaviano L;Ugolini F;Lana D;Bulli I;Magni G;Rossi F;Giovannini MG;Pedata F
脑缺血是一种多因素病理学，其特征首先是由于兴奋性毒性引起的急性损伤，随后是在缺血后数小时至数天发生的继发性脑损伤。在缺血期间，腺苷充当内源性神经保护剂。由于腺苷对A2 B受体的作用强度较低，而且迄今为止开发的选择性配体很少，因此很少有研究探讨A2 B受体在脑缺血中的作用。A2 B受体几乎不存在，但广泛分布于脑中的神经元、神经胶质和内皮细胞以及造血细胞、淋巴细胞和嗜中性粒细胞上，它们主要发挥抗炎作用，抑制血管粘附和炎性细胞迁移。这项工作的目的是验证长期施用A2 B激动剂BAY 60 -6583（0.1mg/kg i. p.，两次/天），在大鼠短暂（1小时）大脑中动脉闭塞（tMCAo）诱导的局灶性缺血后4小时开始，在缺血损伤后具有保护作用。BAY 60 -6583改善了tMCAo后长达7天的神经功能缺损。BAY 60 -6583可明显减轻脑缺血后皮层和纹状体的脑损伤，对抗脑缺血引起的神经元死亡，减少小胶质细胞的活化和星形胶质细胞的改变。降低外周血TNF-α的表达，升高IL-10的表达。缺血后两天，BAY 60 -6583减少了缺血皮质中的血细胞浸润。目前的研究表明，A2 B受体刺激可以减轻缺血后发生的神经炎症，这表明A2 B受体可能代表一个新的有趣的药理学靶点，以防止脑缺血后的变性。
Cerebral ischemia is a multifactorial pathology characterized first by an acute injury, due to excitotoxicity, followed by a secondary brain injury that develops hours to days after ischemia. During ischemia, adenosine acts as an endogenous neuroprotectant. Few studies have investigated the role of A2B receptor in brain ischemia because of the low potency of adenosine for it and the few selective ligands developed so far. A2B receptors are scarcely but widely distributed in the brain on neurons, glial and endothelial cells and on hematopoietic cells, lymphocytes and neutrophils, where they exert mainly anti-inflammatory effects, inhibiting vascular adhesion and inflammatory cells migration. Aim of this work was to verify whether chronic administration of the A2B agonist, BAY60-6583 (0.1 mg/kg i.p., twice/day), starting 4 h after focal ischemia induced by transient (1 h) Middle Cerebral Artery occlusion (tMCAo) in the rat, was protective after the ischemic insult. BAY60-6583 improved the neurological deficit up to 7 days after tMCAo. Seven days after ischemia BAY60-6583 reduced significantly the ischemic brain damage in cortex and striatum, counteracted ischemia-induced neuronal death, reduced microglia activation and astrocytes alteration. Moreover, it decreased the expression of TNF-α and increased that of IL-10 in peripheral plasma. Two days after ischemia BAY60-6583 reduced blood cell infiltration in the ischemic cortex. The present study indicates that A2B receptors stimulation can attenuate the neuroinflammation that develops after ischemia, suggesting that A2B receptors may represent a new interesting pharmacological target to protect from degeneration after brain ischemia.
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影响因子：
5.6
作者：
Eisenstein, Anna;Ravid, Katya
通讯作者：
Ravid, Katya
DOI：
10.1093/brain/awv328
发表时间：
2016-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Chen A;Akinyemi RO;Hase Y;Firbank MJ;Ndung'u MN;Foster V;Craggs LJ;Washida K;Okamoto Y;Thomas AJ;Polvikoski TM;Allan LM;Oakley AE;O'Brien JT;Horsburgh K;Ihara M;Kalaria RN
通讯作者：
Kalaria RN
影响因子：
8.3
作者：
Gelderblom, Mathias;Leypoldt, Frank;Magnus, Tim
通讯作者：
Magnus, Tim
影响因子：
3.7
作者：
Cerbai F;Lana D;Nosi D;Petkova-Kirova P;Zecchi S;Brothers HM;Wenk GL;Giovannini MG
通讯作者：
Giovannini MG
影响因子：
20.3
作者：
Eckle, Tobias;Faigle, Marion;Eltzschig, Holger K.
通讯作者：
Eltzschig, Holger K.