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首页> 外文期刊>Translational Stroke Research >Perlecan Domain V Is Neuroprotective and Affords Functional Improvement in a Photothrombotic Stroke Model in Young and Aged Mice
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Perlecan Domain V Is Neuroprotective and Affords Functional Improvement in a Photothrombotic Stroke Model in Young and Aged Mice

机译：Perlecan域V是年轻的和老年的小鼠的光致血栓性中风模型的神经保护和Affords功能改善。

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摘要

With the failure of so many pre-clinical stroke studies to translate into the clinic, there is a need to find new therapeutics to minimize the extent of cellular damage and aid in functional recovery. Domain V (DV), the c-terminal protein fragment of the vascular basement membrane component, perlecan, was recently shown to afford significant protection in multiple transient middle cerebral artery occlusion stroke models. We sought here to determine whether DV might have similar therapeutic properties in a focal photothrombosis stroke model in both young and aged mice. Young (3-month old) and aged (24-month old) mice underwent photothrombotic stroke to the motor cortex and were then treated with DV or phosphate buffered saline vehicle at different initial time points up to 7 days. Stroke volume was analyzed histologically using cresyl violet and functional recovery assessed behaviorally on both the grid-walking and cylinder tasks. In young mice, DV administration resulted in a significant decrease in infarct volume when treatment started 3 or 6 h post-stroke. In aged mice, DV administration was only protective when started 3 h post-stroke. In addition to a decrease in the area of infarction, DV treatment was effective in significantly decreasing the number of foot-faults on the grid-walking task and improving use of the stroke-affected limb in the cylinder task in both young and aged. Previously, we have shown that DV can alter the expression profile of various astroglial markers. Consistent with our previous finding, treatment groups that showed therapeutic potential in both young and aged mice also showed an elevation in glial fibrillary acidic protein (GFAP) expression in peri-infarct regions. We conclude that DV is neuroprotective and affords significant improvements in functional recovery in both young and aged mice after focal ischemia. These data also highlight a therapeutic time-window shift that is narrower in aged compared with young mice and is associated with an elevation in GFAP expression and heightened astrogliosis.
机译：由于许多临床前中风研究未能转化为临床，因此需要寻找新的疗法来最大程度地减少细胞损伤的程度并帮助功能恢复。域V（DV），是血管基底膜成分c-末端蛋白片段perlecan，最近在多个短暂性大脑中动脉闭塞性中风模型中提供了重要的保护。我们试图在这里确定DV在年轻和老年小鼠的局灶性血栓形成性卒中模型中是否可能具有相似的治疗特性。对年轻（3个月大）和年龄大（24个月大）的小鼠进行光血栓性中风至运动皮层，然后在不同的初始时间点用DV或磷酸盐缓冲盐水载体处理，直至7天。使用甲酚紫通过组织学分析中风量，并通过网格行走和圆柱体任务对行为恢复进行行为评估。在年轻小鼠中，中风后3或6小时开始治疗时，DV的使用会导致梗塞体积的明显减少。在老年小鼠中，仅在中风后3小时才开始DV给药。除了减少梗塞面积之外，DV治疗还可以有效地减少网格行走任务中的踩踏次数，并改善年轻人和老年人在圆筒任务中受中风影响的肢体的使用。以前，我们已经表明DV可以改变各种星形胶质标记的表达谱。与我们先前的发现一致，在年轻和老年小鼠中均显示出治疗潜力的治疗组在梗塞周围区域的神经胶质纤维酸性蛋白（GFAP）表达也有所增加。我们得出的结论是，DV具有神经保护作用，并在局灶性缺血后的年轻和老年小鼠的功能恢复中提供了显着改善。这些数据还强调了治疗时间窗的变化，与年轻小鼠相比，年龄的变化更窄，并且与GFAP表达升高和星形胶质增高相关。

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  • 来源
    《Translational Stroke Research》 |2013年第5期|515-523|共9页
  • 作者

    Gregory J. Bix; Emma K. Gowing; Andrew N. Clarkson;

  • 作者单位

    Anatomy and Neurobiology University of Kentucky College of Medicine Sanders Brown Center for Aging">(1);

    Neurology University of Kentucky College of Medicine Sanders Brown Center for Aging">(2);

    Anatomy University of Otago">(3);

    Brain Health Research Center University of Otago">(5);

    Anatomy University of Otago">(3);

    Psychology University of Otago">(4);

    Brain Health Research Center University of Otago">(5);

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  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    Cerebral infarct; Extracellular matrix; Behavioral recovery;

    机译：脑梗塞;细胞外基质行为恢复;

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