Characterization of tissue and functional deficits in a clinically translational pig model of acute ischemic stroke.

Characterization of tissue and functional deficits in a clinically translational pig model of acute ischemic stroke.
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DOI:
10.1016/j.brainres.2020.146778
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发表时间:
2020-06-01
期刊:
影响因子:
2.9
通讯作者:
--
中科院分区:
医学3区
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--
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急性卒中阶段是用于评估卒中严重程度、治疗选择和预后的关键时间范围,同时也是诊断开发的主要工具。为了进一步了解中风病理生理学并促进治疗的发展,我们的小组开发了转化猪缺血性中风模型。在这项研究中,进一步描述了急性缺血组织损伤、免疫反应和功能缺陷的演变。长白猪大脑中动脉闭塞诱发中风。中风后 24 小时,磁共振成像显示同侧弥散性下降,半球肿胀增加,导致明显的中线移位和脑出血。中风对白质完整性产生负面影响,内囊各向异性分数降低。与患者一样,猪的循环淋巴细胞减少,中性粒细胞和带状细胞激增。通过减少露天探索和时空步态参数的损伤,功能反应与结构变化相对应。猪急性缺血性中风的特征为组织和功能水平评估提供了重要见解,可用于识别潜在的生物标志物并改进新疗法的临床前测试。
The acute stroke phase is a critical time frame used to evaluate stroke severity, therapeutic options, and prognosis while also serving as a major tool for the development of diagnostics. To further understand stroke pathophysiology and to enhance the development of treatments, our group developed a translational pig ischemic stroke model. In this study, the evolution of acute ischemic tissue damage, immune responses, and functional deficits were further characterized. Stroke was induced by middle cerebral artery occlusion in Landrace pigs. At 24 hours post-stroke, magnetic resonance imaging revealed a decrease in ipsilateral diffusivity, an increase in hemispheric swelling resulting in notable midline shift, and intracerebral hemorrhage. Stroke negatively impacted white matter integrity with decreased fractional anisotropy values in the internal capsule. Like patients, pigs showed a reduction in circulating lymphocytes and a surge in neutrophils and band cells. Functional responses corresponded with structural changes through reductions in open field exploration and impairments in spatiotemporal gait parameters. Characterization of acute ischemic stroke in pigs provided important insights into tissue and functional-level assessments that could be used to identify potential biomarkers and improve preclinical testing of novel therapeutics.
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