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首页> 外文期刊>Translational Stroke Research >Superior Neuroprotective Efficacy of LAU-0901, a Novel Platelet-Activating Factor Antagonist, in Experimental Stroke
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Superior Neuroprotective Efficacy of LAU-0901, a Novel Platelet-Activating Factor Antagonist, in Experimental Stroke

机译：新型血小板活化因子拮抗剂LAU-0901在实验性卒中中的卓越神经保护功效

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摘要

Platelet-activating factor (PAF) accumulates during cerebral ischemia, and inhibition of this process plays a critical role in neuronal survival. Recently, we demonstrated that LAU-0901, a novel PAF receptor antagonist, is neuroprotective in experimental stroke. We used magnetic resonance imaging in conjunction with behavior and immunohistopathology to expand our understanding of this novel therapeutic approach. Sprague–Dawley rats received 2 h middle cerebral artery occlusion (MCAo) and were treated with LAU-0901 (60 mg/kg) or vehicle 2 h from MCAo onset. Behavioral function, T2-weighted imaging (T2WI), and apparent diffusion coefficients were performed on days 1, 3, and 7 after MCAo. Infarct volume and number of GFAP, ED-1, and NeuN-positive cells were conducted on day 7. Behavioral deficit was significantly improved by LAU-0901 treatment compared to vehicle on days 1, 3, and 7. Total lesion volumes computed from T2WI were significantly reduced by LAU-0901 on days 1, 3, and 7 (by 83%, 90%, and 96%, respectively), which was consistent with decreased edema formation. Histopathology revealed that LAU-0901 treatment resulted in significant reduction of cortical and subcortical infarct volumes, attenuated microglial infiltration, and promoted astrocytic and neuronal survival. These findings suggest LAU-0901 is a promising neuroprotectant and provide the basis for future therapeutics in patients suffering ischemic stroke.
机译：血小板活化因子（PAF）在脑缺血期间积累，对此过程的抑制在神经元存活中起关键作用。最近，我们证明了新型PAF受体拮抗剂LAU-0901在实验性中风中具有神经保护作用。我们将磁共振成像与行为和免疫组织病理学结合使用，以扩展我们对这种新型治疗方法的理解。 Sprague-Dawley大鼠在大脑中动脉闭塞2 h（MCAo）后2小时内接受LAU-0901（60 mg / kg）或赋形剂治疗。在MCAo后的第1、3和7天进行行为功能，T2加权成像（T2WI）和表观扩散系数。在第7天进行梗塞体积和GFAP，ED-1和NeuN阳性细胞的数目，与在第1、3和7天进行的媒介物相比，通过LAU-0901治疗显着改善了行为缺陷。 LAU-0901在第1天，第3天和第7天显着减少（分别减少83％，90％和96％），这与水肿形成的减少相一致。组织病理学显示，LAU-0901治疗可导致皮质和皮质下梗死体积显着减少，小胶质细胞浸润减弱并促进星形胶质细胞和神经元存活。这些发现表明，LAU-0901是一种有前途的神经保护剂，并为缺血性中风患者的未来治疗提供了基础。

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  • 来源
    《Translational Stroke Research》 |2012年第1期|154-163|共10页
  • 作者

    Ludmila Belayev; Tiffany N. Eady; Larissa Khoutorova; Kristal D. Atkins; Andre Obenaus; Marta Cordoba; Juan J. Vaquero; Julio Alvarez-Builla; Nicolas G. Bazan;

  • 作者单位

    Neuroscience Center of Excellence Louisiana State University Health Sciences Center 2020 Gravier Street Suite D New Orleans LA 70112 USA;

    Neuroscience Center of Excellence Louisiana State University Health Sciences Center 2020 Gravier Street Suite D New Orleans LA 70112 USA;

    Neuroscience Center of Excellence Louisiana State University Health Sciences Center 2020 Gravier Street Suite D New Orleans LA 70112 USA;

    Neuroscience Center of Excellence Louisiana State University Health Sciences Center 2020 Gravier Street Suite D New Orleans LA 70112 USA;

    Non-Invasive Imaging Laboratory Loma Linda University Loma Linda CA USA;

    Depto. de Químíca Organica Universidad de Alcala 28871 Alcala de Henares Madrid Spain;

    Depto. de Químíca Organica Universidad de Alcala 28871 Alcala de Henares Madrid Spain;

    Depto. de Químíca Organica Universidad de Alcala 28871 Alcala de Henares Madrid Spain;

    Neuroscience Center of Excellence Louisiana State University Health Sciences Center 2020 Gravier Street Suite D New Orleans LA 70112 USA;

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  • 正文语种 eng
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  • 关键词

    LAU-0901; PAF antagonist; Magnetic resonance imaging; Middle cerebral artery occlusion; Stroke; Neuroprotection;

    机译：LAU-0901;PAF拮抗剂;磁共振成像;大脑中动脉闭塞;中风;神经保护;

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