Perlecan domain V is neuroprotective and proangiogenic following ischemic stroke in rodents
| Autor: | Anthony Wayne Orr, Abraham Al Ahmad, Boyeon Lee, Lisa D. Auckland, Mehmet Fidanboylu, Andrzej Fertala, Courtney Shaw, Gregory J. Bix, Christi Parham, Sarah A. Thomas, Omolara O. Ogunshola, Michael P. Kahle, Douglas Clarke |
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| Přispěvatelé: | University of Zurich, Bix, G J |
| Rok vydání: | 2012 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Pathology medicine.medical_specialty Angiogenesis Ischemia Perlecan 2700 General Medicine Pharmacology Neuroprotection Models Biological Extracellular matrix Rats Sprague-Dawley Mice medicine Animals Humans cardiovascular diseases Stroke biology Neovascularization Pathologic business.industry Brain General Medicine medicine.disease 10081 Institute of Veterinary Physiology Extracellular Matrix Protein Structure Tertiary Rats Endothelial stem cell Mice Inbred C57BL Vascular endothelial growth factor A Neuroprotective Agents biology.protein 570 Life sciences business Corrigendum Heparan Sulfate Proteoglycans Integrin alpha5beta1 Research Article |
| Zdroj: | Journal of Clinical Investigation. 122:777-777 |
| ISSN: | 0021-9738 |
| Popis: | 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 peri-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 α5β1 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. |
| Databáze: | OpenAIRE |
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