Platelet-activating factor receptor (PAFR) plays a crucial role in experimental global cerebral ischemia and reperfusion
Platelet-activating factor receptor (PAFR) plays a crucial role in experimental global cerebral ischemia and reperfusion
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DOI：
10.1016/j.brainresbull.2016.03.022
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发表时间：
2016-06-01
影响因子：
3.8
通讯作者：
Rachid, Milene Alvarenga
中科院分区：
文献类型：
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作者：
de Brito Toscano, Eliana Cristina;Silva, Bruno Costa;Rachid, Milene Alvarenga
中风是全世界最常见的死亡和残疾原因之一，导致严重的临床和社会经济负担。尽管中风的发病机制涉及不同的机制，但缺血后会发生炎症反应，并导致脑损伤的扩大。血小板激活因子受体（PAF）在大脑的生理和病理条件下发挥着至关重要的作用。 PAF受体(PAFR)可以在多种细胞类型的细胞膜和核膜上表达，特别是白细胞、血小板、内皮细胞、神经元细胞和小胶质细胞。在此，我们使用缺乏 PAFR 受体 (PAFR(-/-)) 的小鼠，研究了该受体在实验性短暂性全脑缺血再灌注 (BCCAo) 过程中的潜在作用。在 PAFR 缺乏症中，我们观察到神经功能缺陷显着改善，这与氯化三苯基四唑 (TTC) 评估的脑梗塞面积减少有关。此外，通过组织计量分析还发现坏死空腔区域的百分比和缺血神经元的频率减少。此外，在 PAFR(-/-) 小鼠中，Caspase-3 激活受到抑制，血管通透性降低，脑水肿减少。通过 ELISA，在 PAFR(-/-) BCCAo 动物中还检测到细胞因子肿瘤坏死因子-α (TNFα)、白细胞介素-1 β (IL-1β) 和趋化因子（C-X-C 基序）配体 1 (CXCL1) 的脑水平降低。综上所述，我们的结果表明 PAFR 激活可能对全脑缺血和再灌注损伤至关重要。 (C) 2016 Elsevier Inc. 保留所有权利。
Stroke is one of the most frequent causes of death and disability worldwide leading to a significant clinical and socioeconomic burden. Although different mechanisms are involved in the pathogenesis of stroke, inflammatory response occurs after ischemia and contributes to the expansion of brain injury. Platelet activating factor receptor (PAF) plays crucial roles in both physiological and pathological conditions in the brain. PAF receptor (PAFR) may be expressed on cellular and nuclear membranes of various cell types, especially leukocytes, platelets, endothelial cells, neuronal cells and microglia. Herein, using mice lacking the PAFR receptor (PAFR(-/-)), we investigate a potential role for this receptor during experimental transient global cerebral ischemia and reperfusion (BCCAo). In PAFR deficiency, we observed a significant improvement in the neurological deficits, which were associated with a reduction of brain infarcted area as evaluated by triphenyltetrazolium chloride (TTC). Moreover, a decrease in the percentage of necrotic cavities areas and in the frequency of ischemic neurons was also found by employing histometric analysis. In addition, in PAFR(-/-) mice there was prevention of caspase-3 activation and decreaied vascular permeability and brain edema. Decreased brain levels of the cytokines tumor necrosis factor-alpha (TNFalpha), interleukin-1 beta (IL-1beta) and the chemokine (C-X-C motif) ligand 1 (CXCL1) by ELISA were also detected in PAFR(-/-) BCCAo animals. Taken together, our results suggest that PAFR activation might be crucial for the global brain ischemia and reperfusion injury. (C) 2016 Elsevier Inc. All rights reserved.