Neuroprotective Effects of Poly(ADP-ribose)polymerase Inhibitor Olaparib in Transient Cerebral Ischemia
Neuroprotective Effects of Poly(ADP-ribose)polymerase Inhibitor Olaparib in Transient Cerebral Ischemia
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聚（ADP-核糖）聚合酶抑制剂奥拉帕尼对短暂性脑缺血的神经保护作用
DOI：
10.1007/s11064-016-1864-6
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发表时间：
2016-02
影响因子：
4.4
通讯作者：
Jin Lingjing
中科院分区：
文献类型：
--
作者：
Teng Fei;Zhu Ling;Su Junhui;Zhang Xi;Li Ning;Nie Zhiyu;Jin Lingjing
奥拉帕尼是第一个被美国食品和药物管理局批准用于肿瘤治疗的聚（ADP-核糖）聚合酶抑制剂。然而，其神经保护作用尚未阐明。本研究旨在评价奥拉帕尼在短暂性脑缺血中的作用。使用短暂性大脑中动脉闭塞的小鼠模型。缺血后2 h进行再灌注。再灌注后立即腹腔注射不同剂量的奥拉帕尼（1、3、5、10和25 mg/kg）。缺血后24小时，评估神经学评分，并进行抓握和绳测试以评估小鼠的行为缺陷。甲酚紫染色观察脑水肿程度及病灶体积。进行免疫组织化学以评估血脑屏障蛋白IV型胶原和紧密连接蛋白-5的表达以及IgG的外渗。缺血诱导神经功能缺损，奥拉帕尼在3和5 mg/kg剂量下显著改善。然而，在用低剂量或高剂量奥拉帕尼治疗的小鼠中没有观察到这种神经保护作用。3和5 mg/kg奥拉帕尼均显着减少脑梗死体积，但不减少脑水肿。脑缺血后IV型胶原表达减少，3和5 mg/kg的olaparib可改善IV型胶原的表达。这些结果通过奥拉帕尼减少IgG外渗得到证实。奥拉帕尼对短暂性脑缺血小鼠表现出明显的神经保护作用，主要通过减少脑梗死和血脑屏障损伤。
Olaparib was the first poly(ADP-ribose)polymerase inhibitor approved by Food and Drug Administration for oncology treatment. However, its neuroprotective effects have not been elucidated. This study aimed to evaluate the effects of olaparib in transient cerebral ischemia. A mouse model of transient middle cerebral artery occlusion was used. Reperfusion was performed at 2 h after ischemia. Different doses of olaparib (1, 3, 5, 10 and 25 mg/kg) were administered intraperitoneally immediately after reperfusion. Twenty-four hours after ischemia, the neurological score was assessed, and grip and string tests were performed to evaluate the behavioral deficits in the mice. Cresyl violet staining was used to assess cerebral edema and the lesion volume. Immunohistochemistry was performed to evaluate the expression of blood–brain barrier proteins collagen IV and claudin-5, as well as extravasation.of IgG. Ischemia induced a neurological deficit, which was significantly ameliorated by olaparib at 3 and 5 mg/kg. However, this neuroprotective effect was not observed in mice treated with either low-dose or high-dose olaparib. Both 3 and 5 mg/kg olaparib markedly reduced cerebral infarction volume, but not cerebral edema. The expression of collagen IV decreased after cerebral ischemia, which was improved by olaparib at 3 and 5 mg/kg. These results.were confirmed by the reduction of IgG extravasation with olaparib. Olaparib showed clear neuroprotective effects in transient ischemic mice mainly through the reduction of cerebral infarction and blood–brain barrier damage.
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影响因子：
5.3
作者：
F. Teng;V. Beray-Berthat;B. Coqueran;Clémentine Lesbats;Mélanie Kuntz;B. Palmier;Marie Garraud;Cyrielle Bedfert;Niamh Slane;V. Bérézowski;F. Szeremeta;J. Hachani;D. Scherman;M. Plotkine;B. Doan;C. Marchand-Leroux;I. Margaill
通讯作者：
F. Teng;V. Beray-Berthat;B. Coqueran;Clémentine Lesbats;Mélanie Kuntz;B. Palmier;Marie Garraud;Cyrielle Bedfert;Niamh Slane;V. Bérézowski;F. Szeremeta;J. Hachani;D. Scherman;M. Plotkine;B. Doan;C. Marchand-Leroux;I. Margaill
DOI：
--
发表时间：
2008-12
期刊：
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society
影响因子：
--
作者：
S. Hendryk;Z. Czuba;H. Jędrzejowska‐Szypułka;E. Szliszka;V. Phillips;M. Threadgill;W. Krol
通讯作者：
S. Hendryk;Z. Czuba;H. Jędrzejowska‐Szypułka;E. Szliszka;V. Phillips;M. Threadgill;W. Krol
影响因子：
168.9
作者：
Lozano, Rafael;Naghavi, Mohsen;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.
影响因子：
7.3
作者：
F. Moroni;A. Cozzi;A. Chiarugi;L. Formentini;E. Camaioni;D. Pellegrini-Giampietro;Yi Chen;S. Liang-S.
通讯作者：
F. Moroni;A. Cozzi;A. Chiarugi;L. Formentini;E. Camaioni;D. Pellegrini-Giampietro;Yi Chen;S. Liang-S.
影响因子：
45.3
作者：
Fong, Peter C.;Yap, Timothy A.;Kaye, Stan B.
通讯作者：
Kaye, Stan B.