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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\u003Cp id=\u0022p-1\u0022\u003EPerlecan domain V (DV) may improve functional stroke outcome. This article discusses findings from a study that investigated the effect of the extracellular matrix fragment perlecan domain V on angiogenesis and neurogenesis in poststroke rats and mice.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eneurology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ecerebrovascular disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eneurology clinical trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\u003Cp id=\u0022p-2\u0022\u003EPerlecan domain V (DV) may improve functional stroke outcome. Boyeon Lee, PhD, Texas A\u0026amp;M College of Medicine, College Station, TX, presented findings from a study that investigated the effect of the extracellular matrix (ECM) fragment perlecan domain V on angiogenesis and neurogenesis in poststroke rats and mice.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ENeurovascular coupling of angiogenesis and neurogenesis has been shown to involve ECM remodeling and ECM fragment initiation [Ohab JJ et al. \u003Cem\u003EJ Neuroscience\u003C\/em\u003E 2006]. Additionally, DV has been shown to interact with the ECM and promote angiogenesis [Segev A et al. \u003Cem\u003ECardiovasc Res\u003C\/em\u003E 2004; Mongiat M et al. \u003Cem\u003EJ Biol Chem\u003C\/em\u003E 2003]. In this study by Lee and colleagues, sham surgery control was performed or transient middle cerebral artery occlusive stroke was induced by using sterotactic injection of endothelin-1 in rats or tandem ipsilateral common carotid artery and middle cerebral artery occlusion in mice. All subjects received either intraperitoneal injections of human recombinant DV 0.5\u20131 mg\/kg or phosphate-buffered saline control at Days 1, 3, 5, and 7 poststroke (n=15 for each group). Functional use of the affected limb was determined by the vibrissae-elicited paw placement reflex in mice and the cylinder test in rats. Concurrent brain microvascular endothelial cell \u003Cem\u003Ein vitro\u003C\/em\u003E studies were also performed to evaluate the effect of DV on angiogenesis.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EBrain immunohistochemistry (von Willebrand factor) demonstrated that perlecan DV homed to the stroke and peri-infarct vasculature. DV was significantly higher in the stroked cerebral hemisphere at Days 1, 3, 5, and 7 poststroke compared with corresponding contralateral hemisphere levels (Day 1 p=0.0001; Day 3 p=0.0007; Day 5 p=0.007; Day 7 p=0.005). Additionally, subjects that were treated with DV had more neurons with normal morphology and lower incidence of TUNEL-positive cells or shrunken and misshapen cells, suggesting a neuroprotective component that was associated with DV. DV treatment was associated with increased poststroke neurogenesis and poststroke angiogenesis. Significant increases were observed in stroke peri-infarct vasculature in subjects that were treated with DV on poststroke Days 3, 5, and 7 versus control (p=0.001; p\u0026lt;0.00001; p\u0026lt;0.00001 for Days 3, 5, and 7, respectively). DV treatment also resulted in significantly more doublecortin-positive pixels on poststroke Days 3, 5, and 7 versus control (Day 3, p=0.00001; Day 5, p\u0026lt;0.00001; Day 7, p\u0026lt;0.00001, resulting in enhanced poststroke neurogenesis.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EFunctional stroke outcome was significantly better in stroked subjects that were treated with DV versus control, and improvement in contralateral paw use was observed at Days 3 (p=0.03) and 7 (p=0.009) poststroke. While significant contralateral forelimb improvement was noted in those that were treated with DV, PBS control subjects remained significantly impaired at poststroke Days 3 (p=0.008), 5 (p=0.006), and 7 (p=0.005).\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe \u003Cem\u003Ein vitro\u003C\/em\u003E analysis that was included in this study revealed possible mechanisms by which DV affects angiogenesis. At 3 days poststroke, an increase in \u03b15\u03b21 levels was noted in those that were treated with DV. DV enhances brain endothelial cell formation, which may be inhibited via \u03b15\u03b21. In \u03b15\u03b21 and DV coimmunohistochemistry of brain endothelial cells, colocalization of DV and \u03b15\u03b21 was identified. DV also induces brain endothelial cell VEGF synthesis and release via the \u03b15\u03b21 integrin. A DV dose-dependent VEGF response was noted \u003Cem\u003Ein vitro\u003C\/em\u003E.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EDr. Lee concluded that DV is neuroprotective and promotes poststroke angiogenesis and neurogenesis, thus, contributing to improved functional stroke outcome. DV-induced VEGF release via the \u03b15\u03b21 integrin pathway plays a role in the DV angiogenesis and neurogenesis. However, the extent of their involvement remains unclear. Results from this study are promising and suggest that perlecan DV may provide a viable treatment option for stroke in the future.\u003C\/p\u003E\u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2010 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/10\/1\/20.1.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmua1\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}