期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 121, 期 8, 页码 3005-3023出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI46358
关键词
-
资金
- American Heart Association
- Ted Nash Long Life Foundation
- Texas AM funding
- NIH [R01NS065842-01A01, 5R01AR049537-06, 5R01AR048544]
- BBSRC [BB/E527098/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E527098/1] Funding Source: researchfish
Stroke is the leading cause of long-term disability and the third leading cause of death in the United States. While most research thus far has focused on acute stroke treatment and neuroprotection, the exploitation of endogenous brain self-repair mechanisms may also yield therapeutic strategies. Here, we describe a distinct type of stroke treatment, the naturally occurring extracellular matrix fragment of perlecan, domain V, which we found had neuroprotective properties and enhanced post-stroke angiogenesis, a key component of brain repair, in rodent models of stroke. In both rat and mouse models, Western blot analysis revealed elevated levels of perlecan domain V. When systemically administered 24 hours after stroke, domain V was well tolerated, reached infarct and pen-infarct brain vasculature, and restored stroke-affected motor function to baseline pre-stroke levels in these multiple stroke models in both mice and rats. Post-stroke domain V administration increased VEGF levels via a mechanism involving brain endothelial cell alpha 5 beta 1 integrin, and the subsequent neuroprotective and angiogenic actions of domain V were in turn mediated via VEGFR. These results suggest that perlecan domain V represents a promising approach for stroke treatment.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据