Platelet-activating factor antagonist (ABT-491) decreases neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury
Platelet-activating factor antagonist (ABT-491) decreases neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury
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DOI：
10.1016/j.brainres.2007.01.094
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发表时间：
2007-04-27
期刊：
影响因子：
2.9
通讯作者：
Taskinlar, Hakan
中科院分区：
文献类型：
--
作者：
Bozlu, Gulcin;Atici, Aytug;Taskinlar, Hakan
新生儿缺氧缺血性脑损伤(HIBI)是新生儿死亡和发病的常见原因。到目前为止，还没有研究血小板活化因子(PAF)拮抗剂对新生大鼠HIBI模型神经细胞凋亡的影响。在本研究中，我们观察了高效选择性PAF拮抗剂(ABT-491)对新生大鼠HIBI模型神经细胞凋亡的影响。7日龄Wistar大鼠右颈总动脉结扎，低氧(92%氮和8%氧)2 h，缺氧前或缺氧后即刻分别给予ABT-491或生理盐水处理。假手术组动物既不结扎，也不缺氧。用末端转移酶介导的dUTP生物素缺口末端标记法和caspase-3染色方法检测神经细胞的凋亡。与生理盐水组相比，缺氧前或缺氧后给予ABT-491均可显著减少大鼠双侧大脑半球的凋亡细胞数。各组大鼠右侧大脑半球的凋亡细胞数均明显高于左侧。这些结果表明，ABT-491是一种高效、选择性的PAF拮抗剂，在缺氧前或缺氧后应用均可减少细胞凋亡，我们认为ABT-491可能是治疗HIBI的一种新方法。(C)2007 Elsevier B.V.保留所有权利。
Hypoxic ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. To date, no study has investigated the role of platelet-activating factor (PAF) antagonists on neuronal apoptosis in neonatal rat model of HIBI. In the present study, we evaluated the effect of a highly potent and selective PAF antagonist (ABT-491) on neuronal apoptosis in neonatal rat model of HIBI. Seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia (92% nitrogen and 8% oxygen) for 2 h. They were treated with ABT-491 or saline either immediately before or after hypoxia. In sham group animals, neither ligation, nor hypoxia was performed. Neuronal apoptosis was evaluated by the terminal-transferase mediated dUTP biotin nick-end-labeling (TUNEL) and caspase-3 staining methods. Administration of ABT-491 either before or after hypoxia resulted in significant reduction of the numbers of apoptotic cells in both hemispheres, when compared to saline treatment group. The numbers of apoptotic cells in right hemispheres in all groups were significantly higher than that in the left hemispheres. These results suggested that ABT-491, a highly potent and selective PAF antagonist, administration either before or after hypoxia reduces apoptosis and we propose that ABT-491 may be a novel approach in the treatment of HIBI. (c) 2007 Elsevier B.V. All rights reserved.