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Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats
Physical and chemical constraints imposed by the periinfarct glial scar may contribute to the limited clinical improvement often observed after ischemie brain injury. To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chon...
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| Published in: | Proceedings of the National Academy of Sciences - PNAS 2012-06, Vol.109 (23), p.9155-9160 |
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| container_issue | 23 |
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| creator | Hill, Justin J. Jin, Kunlin Mao, Xiao Ou Xie, Lin Greenberg, David A. |
| description | Physical and chemical constraints imposed by the periinfarct glial scar may contribute to the limited clinical improvement often observed after ischemie brain injury. To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate proteoglycan neurocan, thegrowth-stimulating heparan sulfate proteoglycan glypican, or the chondroitin sulfate proteoglycandegrading enzyme chondroitinase ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion. Glypican and chondroitinase ABC reduced glial fibrillary acidic protein immunoreactivity and increased microtubule-associated protein-2 ¡ mmunoreactivity in the periinfarct region, and glypican-and chondroitinase ABC-treated rats showed behavioral improvement compared with neurocan-or saline-treated rats. Glypican and chondroitinase ABC also increased neurite extension in cortical neuron cultures. Glypican increased fibroblast growth factor-2 expression and chondroitinase ABC increased brain-derived neurotrophic factor expression in these cultures, whereas no such effects were seen following neurocan treatment. Thus, treatment with glypican or enzymatic disruption of neurocan with chondroitinase ABC improves gross anatomical, histological, and functional outcome in the chronic phase of experimental stroke in rats. Changes in growth factor expression and neuritogenesis may help to mediate these effects. |
| doi_str_mv | 10.1073/pnas.1205697109 |
| format | article |
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To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate proteoglycan neurocan, thegrowth-stimulating heparan sulfate proteoglycan glypican, or the chondroitin sulfate proteoglycandegrading enzyme chondroitinase ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion. Glypican and chondroitinase ABC reduced glial fibrillary acidic protein immunoreactivity and increased microtubule-associated protein-2 ¡ mmunoreactivity in the periinfarct region, and glypican-and chondroitinase ABC-treated rats showed behavioral improvement compared with neurocan-or saline-treated rats. Glypican and chondroitinase ABC also increased neurite extension in cortical neuron cultures. Glypican increased fibroblast growth factor-2 expression and chondroitinase ABC increased brain-derived neurotrophic factor expression in these cultures, whereas no such effects were seen following neurocan treatment. Thus, treatment with glypican or enzymatic disruption of neurocan with chondroitinase ABC improves gross anatomical, histological, and functional outcome in the chronic phase of experimental stroke in rats. Changes in growth factor expression and neuritogenesis may help to mediate these effects.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1205697109</identifier><identifier>PMID: 22615373</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Animals ; Antibodies ; Astrocytes ; Behavioral neuroscience ; Biological Sciences ; Blotting, Western ; Brain damage ; Brain-Derived Neurotrophic Factor - metabolism ; Central nervous system ; Chondroitin ABC Lyase - administration & dosage ; Chondroitin ABC Lyase - pharmacology ; Chondroitin ABC Lyase - therapeutic use ; Fibroblast Growth Factor 2 - metabolism ; Gene expression ; Glial Fibrillary Acidic Protein - immunology ; Glypicans ; Glypicans - administration & dosage ; Glypicans - pharmacology ; Glypicans - therapeutic use ; Immunohistochemistry ; Infusions, Intra-Arterial ; Ischemia ; Microtubule-Associated Proteins - immunology ; Neurites ; Neurites - drug effects ; Neurocan - administration & dosage ; Neurocan - pharmacology ; Neurocan - therapeutic use ; Neurons ; Proteins ; Psychomotor Performance - drug effects ; Rats ; Rats, Sprague-Dawley ; Rodents ; Scars ; Spinal cord ; Stroke ; Stroke - drug therapy ; Stroke - enzymology ; Strokes</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2012-06, Vol.109 (23), p.9155-9160</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Jun 5, 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-333b690b197d34f510440b25ce1da8fddb478a7a06027856ce2791a3ba8496c43</citedby><cites>FETCH-LOGICAL-c533t-333b690b197d34f510440b25ce1da8fddb478a7a06027856ce2791a3ba8496c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/109/23.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41603067$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41603067$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,730,783,787,888,27937,27938,53805,53807,58571,58804</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22615373$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hill, Justin J.</creatorcontrib><creatorcontrib>Jin, Kunlin</creatorcontrib><creatorcontrib>Mao, Xiao Ou</creatorcontrib><creatorcontrib>Xie, Lin</creatorcontrib><creatorcontrib>Greenberg, David A.</creatorcontrib><title>Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Physical and chemical constraints imposed by the periinfarct glial scar may contribute to the limited clinical improvement often observed after ischemie brain injury. To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate proteoglycan neurocan, thegrowth-stimulating heparan sulfate proteoglycan glypican, or the chondroitin sulfate proteoglycandegrading enzyme chondroitinase ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion. Glypican and chondroitinase ABC reduced glial fibrillary acidic protein immunoreactivity and increased microtubule-associated protein-2 ¡ mmunoreactivity in the periinfarct region, and glypican-and chondroitinase ABC-treated rats showed behavioral improvement compared with neurocan-or saline-treated rats. Glypican and chondroitinase ABC also increased neurite extension in cortical neuron cultures. Glypican increased fibroblast growth factor-2 expression and chondroitinase ABC increased brain-derived neurotrophic factor expression in these cultures, whereas no such effects were seen following neurocan treatment. Thus, treatment with glypican or enzymatic disruption of neurocan with chondroitinase ABC improves gross anatomical, histological, and functional outcome in the chronic phase of experimental stroke in rats. Changes in growth factor expression and neuritogenesis may help to mediate these effects.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Astrocytes</subject><subject>Behavioral neuroscience</subject><subject>Biological Sciences</subject><subject>Blotting, Western</subject><subject>Brain damage</subject><subject>Brain-Derived Neurotrophic Factor - metabolism</subject><subject>Central nervous system</subject><subject>Chondroitin ABC Lyase - administration & dosage</subject><subject>Chondroitin ABC Lyase - pharmacology</subject><subject>Chondroitin ABC Lyase - therapeutic use</subject><subject>Fibroblast Growth Factor 2 - metabolism</subject><subject>Gene expression</subject><subject>Glial Fibrillary Acidic Protein - immunology</subject><subject>Glypicans</subject><subject>Glypicans - administration & dosage</subject><subject>Glypicans - pharmacology</subject><subject>Glypicans - therapeutic use</subject><subject>Immunohistochemistry</subject><subject>Infusions, Intra-Arterial</subject><subject>Ischemia</subject><subject>Microtubule-Associated Proteins - immunology</subject><subject>Neurites</subject><subject>Neurites - drug effects</subject><subject>Neurocan - administration & dosage</subject><subject>Neurocan - pharmacology</subject><subject>Neurocan - therapeutic use</subject><subject>Neurons</subject><subject>Proteins</subject><subject>Psychomotor Performance - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Scars</subject><subject>Spinal cord</subject><subject>Stroke</subject><subject>Stroke - drug therapy</subject><subject>Stroke - enzymology</subject><subject>Strokes</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNpdkc1v1DAQxSMEokvhzAmwxIXLtuPY8ccFqaxaqFSJC5wtx3G6XhI72M5K_e9x2GULXGZG4988-elV1WsMFxg4uZy8The4hoZJjkE-qVal4jWjEp5WK4CarwWt6Vn1IqUdAMhGwPPqrK4Zbggnq2p_63PUxkbbRj0gsw2-i8FlV4Qtuvq0Qdp3aGsnHbVHaR56nS2aYsg23A8PpixLm9wyuLHs9xaFOZswWtTHMBbFGLwzKOUYfljkPIo6p5fVs14Pyb469vPq-831t82X9d3Xz7ebq7u1aQjJa0JIyyS0WPKO0L7BQCm0dWMs7rTou66lXGiugRWnomHG1lxiTVotqGSGkvPq40F3mtvRdsYubgc1RTfq-KCCdurfF--26j7sFSGCYgZF4MNRIIafs01ZjS4ZOwza2zAnhQFLkIJLUtD3_6G7MEdf7C2UkIJJvFCXB8rEkFK0_ekzGNSSqVoyVY-Zlou3f3s48X9CLMC7I7BcPspJVRMlcdMU4s2B2KUc4gn57RAYJ78AyDezSg</recordid><startdate>20120605</startdate><enddate>20120605</enddate><creator>Hill, Justin J.</creator><creator>Jin, Kunlin</creator><creator>Mao, Xiao Ou</creator><creator>Xie, Lin</creator><creator>Greenberg, David A.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120605</creationdate><title>Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats</title><author>Hill, Justin J. ; Jin, Kunlin ; Mao, Xiao Ou ; Xie, Lin ; Greenberg, David A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c533t-333b690b197d34f510440b25ce1da8fddb478a7a06027856ce2791a3ba8496c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Astrocytes</topic><topic>Behavioral neuroscience</topic><topic>Biological Sciences</topic><topic>Blotting, Western</topic><topic>Brain damage</topic><topic>Brain-Derived Neurotrophic Factor - metabolism</topic><topic>Central nervous system</topic><topic>Chondroitin ABC Lyase - administration & dosage</topic><topic>Chondroitin ABC Lyase - pharmacology</topic><topic>Chondroitin ABC Lyase - therapeutic use</topic><topic>Fibroblast Growth Factor 2 - metabolism</topic><topic>Gene expression</topic><topic>Glial Fibrillary Acidic Protein - immunology</topic><topic>Glypicans</topic><topic>Glypicans - administration & dosage</topic><topic>Glypicans - pharmacology</topic><topic>Glypicans - therapeutic use</topic><topic>Immunohistochemistry</topic><topic>Infusions, Intra-Arterial</topic><topic>Ischemia</topic><topic>Microtubule-Associated Proteins - immunology</topic><topic>Neurites</topic><topic>Neurites - drug effects</topic><topic>Neurocan - administration & dosage</topic><topic>Neurocan - pharmacology</topic><topic>Neurocan - therapeutic use</topic><topic>Neurons</topic><topic>Proteins</topic><topic>Psychomotor Performance - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Scars</topic><topic>Spinal cord</topic><topic>Stroke</topic><topic>Stroke - drug therapy</topic><topic>Stroke - enzymology</topic><topic>Strokes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hill, Justin J.</creatorcontrib><creatorcontrib>Jin, Kunlin</creatorcontrib><creatorcontrib>Mao, Xiao Ou</creatorcontrib><creatorcontrib>Xie, Lin</creatorcontrib><creatorcontrib>Greenberg, David A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hill, Justin J.</au><au>Jin, Kunlin</au><au>Mao, Xiao Ou</au><au>Xie, Lin</au><au>Greenberg, David A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2012-06-05</date><risdate>2012</risdate><volume>109</volume><issue>23</issue><spage>9155</spage><epage>9160</epage><pages>9155-9160</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Physical and chemical constraints imposed by the periinfarct glial scar may contribute to the limited clinical improvement often observed after ischemie brain injury. To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate proteoglycan neurocan, thegrowth-stimulating heparan sulfate proteoglycan glypican, or the chondroitin sulfate proteoglycandegrading enzyme chondroitinase ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion. Glypican and chondroitinase ABC reduced glial fibrillary acidic protein immunoreactivity and increased microtubule-associated protein-2 ¡ mmunoreactivity in the periinfarct region, and glypican-and chondroitinase ABC-treated rats showed behavioral improvement compared with neurocan-or saline-treated rats. Glypican and chondroitinase ABC also increased neurite extension in cortical neuron cultures. Glypican increased fibroblast growth factor-2 expression and chondroitinase ABC increased brain-derived neurotrophic factor expression in these cultures, whereas no such effects were seen following neurocan treatment. Thus, treatment with glypican or enzymatic disruption of neurocan with chondroitinase ABC improves gross anatomical, histological, and functional outcome in the chronic phase of experimental stroke in rats. Changes in growth factor expression and neuritogenesis may help to mediate these effects.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>22615373</pmid><doi>10.1073/pnas.1205697109</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies Astrocytes Behavioral neuroscience Biological Sciences Blotting, Western Brain damage Brain-Derived Neurotrophic Factor - metabolism Central nervous system Chondroitin ABC Lyase - administration & dosage Chondroitin ABC Lyase - pharmacology Chondroitin ABC Lyase - therapeutic use Fibroblast Growth Factor 2 - metabolism Gene expression Glial Fibrillary Acidic Protein - immunology Glypicans Glypicans - administration & dosage Glypicans - pharmacology Glypicans - therapeutic use Immunohistochemistry Infusions, Intra-Arterial Ischemia Microtubule-Associated Proteins - immunology Neurites Neurites - drug effects Neurocan - administration & dosage Neurocan - pharmacology Neurocan - therapeutic use Neurons Proteins Psychomotor Performance - drug effects Rats Rats, Sprague-Dawley Rodents Scars Spinal cord Stroke Stroke - drug therapy Stroke - enzymology Strokes |
| title | Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats |
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