Perlecan domain V is neuroprotective and affords functional improvement in a photothrombotic stroke model in young and aged mice.
Perlecan domain V is neuroprotective and affords functional improvement in a photothrombotic stroke model in young and aged mice.
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DOI：
10.1007/s12975-013-0266-1
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发表时间：
2013-10
影响因子：
6.9
通讯作者：
Clarkson, Andrew N.
中科院分区：
文献类型：
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作者：
Bix, Gregory J.;Gowing, Emma K.;Clarkson, Andrew N.
由于许多临床前的中风研究未能转化为临床，因此有必要找到新的治疗方法，以尽量减少细胞损伤的程度，并帮助功能恢复。结构域V （DV）是血管基底膜组分perlecan的c端蛋白片段，最近被证明在多种短暂性大脑中动脉闭塞性卒中模型中具有显著的保护作用。我们在这里试图确定DV是否在年轻和老年小鼠局灶性光血栓性卒中模型中具有相似的治疗特性。年幼（3个月大）和年老（24个月大）小鼠在运动皮质发生光血栓性中风，然后在不同的初始时间点用DV或磷酸盐缓冲盐水溶液治疗，直至7天。用甲酚紫对脑卒中容量进行组织学分析，并对网格行走和圆柱体任务的功能恢复进行行为评估。在年轻小鼠中，当中风后3或6小时开始治疗时，DV给药导致梗死体积显著减少。在老年小鼠中，只有在中风后3小时开始给药才有保护作用。除了减少梗死面积外，DV治疗在显著减少网格行走任务中的脚断层数量和改善年轻人和老年人在圆柱形任务中对中风影响肢体的使用方面都是有效的。以前，我们已经证明DV可以改变各种星形胶质细胞标记物的表达谱。与我们之前的发现一致，在年轻和老年小鼠中显示治疗潜力的治疗组也显示梗死周围区域胶质纤维酸性蛋白（GFAP）表达升高。我们得出结论，DV具有神经保护作用，并能显著改善局灶性缺血后年轻和老年小鼠的功能恢复。这些数据还强调，与年轻小鼠相比，老年小鼠的治疗时间窗移位更窄，并且与GFAP表达升高和星形胶质细胞增生加剧有关。
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.
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DOI：
10.1016/s1052-3057(03)00042-9
发表时间：
2003-05-01
期刊：
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
影响因子：
--
作者：
Kelly-Hayes, Margaret;Beiser, Alexa;Wolf, Philip A
通讯作者：
Wolf, Philip A
影响因子：
5.3
作者：
Ohab, John J.;Fleming, Sheila;Carmichael, S. Thomas
通讯作者：
Carmichael, S. Thomas
影响因子：
5.1
作者：
Truelsen, T.;Piechowski-Jozwiak, B.;Boysen, G.
通讯作者：
Boysen, G.
DOI：
10.1093/jnci/djj441
发表时间：
2006-11-15
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Bix, Gregory;Castello, Remedios;Iozzo, Renato V.
通讯作者：
Iozzo, Renato V.
影响因子：
64.8
作者：
通讯作者：
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