{"id":323,"date":"2021-01-07T00:47:35","date_gmt":"2021-01-06T19:47:35","guid":{"rendered":"http:\/\/curesteps.org\/SCI\/?p=323"},"modified":"2021-01-07T00:47:38","modified_gmt":"2021-01-06T19:47:38","slug":"sustained-delivery-of-thermostabilized-chabc-enhances-axonal-sprouting-and-functional-recovery-after-spinal-cord-injury","status":"publish","type":"post","link":"http:\/\/curesteps.org\/SCI\/sustained-delivery-of-thermostabilized-chabc-enhances-axonal-sprouting-and-functional-recovery-after-spinal-cord-injury\/","title":{"rendered":"Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury"},"content":{"rendered":"\n<p><a href=\"https:\/\/www.pnas.org\/content\/107\/8\/3340\">Link<\/a><\/p>\n\n\n\n<h2 class=\"wp-block-heading\">Abstract<\/h2>\n\n\n\n<p id=\"p-3\">Chondroitin sulfate proteoglycans (CSPGs) are a major class of axon growth inhibitors that are up-regulated after spinal cord injury (SCI) and contribute to regenerative failure. Chondroitinase ABC (chABC) digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. But chABC loses its enzymatic activity rapidly at 37 \u00b0C, necessitating the use of repeated injections or local infusions for a period of days to weeks. These infusion systems are invasive, infection-prone, and clinically problematic. To overcome this limitation, we have thermostabilized chABC and developed a system for its sustained local delivery in vivo, obviating the need for chronically implanted catheters and pumps. Thermostabilized chABC remained active at 37 \u00b0C in vitro for up to 4 weeks. CSPG levels remained low in vivo up to 6 weeks post-SCI when thermostabilized chABC was delivered by a hydrogel-microtube scaffold system. Axonal growth and functional recovery following the sustained local release of thermostabilized chABC versus a single treatment of unstabilized chABC demonstrated significant differences in CSPG digestion. Animals treated with thermostabilized chABC in combination with sustained neurotrophin-3 delivery showed significant improvement in locomotor function and enhanced growth of cholera toxin B subunit\u2013positive sensory axons and sprouting of serotonergic fibers. Therefore, improving chABC thermostability facilitates minimally invasive, sustained, local delivery of chABC that is potentially effective in overcoming CSPG-mediated regenerative failure. Combination therapy with thermostabilized chABC with neurotrophic factors enhances axonal regrowth, sprouting, and functional recovery after SCI.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Link Abstract Chondroitin sulfate proteoglycans (CSPGs) are a major class of axon growth inhibitors that are up-regulated after spinal cord injury (SCI) and contribute to regenerative failure. Chondroitinase ABC (chABC) digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. But chABC loses its enzymatic activity rapidly at 37 \u00b0C, necessitating the use of [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[21],"class_list":["post-323","post","type-post","status-publish","format-standard","hentry","category-scar-mitigation","tag-chondroitinase"],"_links":{"self":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts\/323","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/comments?post=323"}],"version-history":[{"count":1,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts\/323\/revisions"}],"predecessor-version":[{"id":324,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/posts\/323\/revisions\/324"}],"wp:attachment":[{"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/media?parent=323"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/categories?post=323"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/curesteps.org\/SCI\/wp-json\/wp\/v2\/tags?post=323"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}