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Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury
Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created...
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Published in: | The Journal of neuroscience 2008-04, Vol.28 (14), p.3814-3823 |
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container_title | The Journal of neuroscience |
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creator | Tysseling-Mattiace, Vicki M Sahni, Vibhu Niece, Krista L Birch, Derin Czeisler, Catherine Fehlings, Michael G Stupp, Samuel I Kessler, John A |
description | Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces. |
doi_str_mv | 10.1523/JNEUROSCI.0143-08.2008 |
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These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.0143-08.2008</identifier><identifier>PMID: 18385339</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Analysis of Variance ; Animals ; Apoptosis - drug effects ; Axons - drug effects ; Axons - physiology ; Caspase 3 - metabolism ; Cicatrix - drug therapy ; Diagnostic Imaging - methods ; Disease Models, Animal ; Female ; Glial Fibrillary Acidic Protein - metabolism ; Gliosis - drug therapy ; Laminin - metabolism ; Laminin - therapeutic use ; Mice ; Motor Neurons - pathology ; Nerve Regeneration - drug effects ; Neuroglia - drug effects ; Peptide Fragments - metabolism ; Peptide Fragments - therapeutic use ; Recovery of Function - drug effects ; Spinal Cord Injuries - drug therapy ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - physiopathology ; Time Factors</subject><ispartof>The Journal of neuroscience, 2008-04, Vol.28 (14), p.3814-3823</ispartof><rights>Copyright © 2008 Society for Neuroscience 0270-6474/08/283814-10$15.00/0 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c594t-a134122e318a691a972540657e39730e950beadd31ef85eae4cc5915c4966c493</citedby><cites>FETCH-LOGICAL-c594t-a134122e318a691a972540657e39730e950beadd31ef85eae4cc5915c4966c493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752951/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752951/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18385339$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tysseling-Mattiace, Vicki M</creatorcontrib><creatorcontrib>Sahni, Vibhu</creatorcontrib><creatorcontrib>Niece, Krista L</creatorcontrib><creatorcontrib>Birch, Derin</creatorcontrib><creatorcontrib>Czeisler, Catherine</creatorcontrib><creatorcontrib>Fehlings, Michael G</creatorcontrib><creatorcontrib>Stupp, Samuel I</creatorcontrib><creatorcontrib>Kessler, John A</creatorcontrib><title>Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.</description><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Axons - drug effects</subject><subject>Axons - physiology</subject><subject>Caspase 3 - metabolism</subject><subject>Cicatrix - drug therapy</subject><subject>Diagnostic Imaging - methods</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Gliosis - drug therapy</subject><subject>Laminin - metabolism</subject><subject>Laminin - therapeutic use</subject><subject>Mice</subject><subject>Motor Neurons - pathology</subject><subject>Nerve Regeneration - drug effects</subject><subject>Neuroglia - drug effects</subject><subject>Peptide Fragments - metabolism</subject><subject>Peptide Fragments - therapeutic use</subject><subject>Recovery of Function - drug effects</subject><subject>Spinal Cord Injuries - drug therapy</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>Time Factors</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNpVkV9r2zAUxcXYaLOuX6H4aXtydvXHtvwyCCHtMkpbmvVZyPZ1oiJLmeQ067efQkK3veiCzu8ciXsIuaIwpQXjX3_cLZ4e71fz5RSo4DnIKQOQ78gkqXXOBND3ZAKsgrwUlTgnH2N8BoAKaHVGzqnksuC8nhC7QtvnsxhxaKxx6-xOO9-bBkPMlm5jGjNmN9Zom61aHbJrHwY9Gu8y7brsIfjBj5jNfqeLhfVufdL6EUO22hqXfHMfuhT1vAuvn8iHXtuIl6d5QZ6uFz_n3_Pb-5vlfHabt0UtxlxTLihjyKnUZU11XbFCQFlUyOuKA9YFNKi7jlPsZYEaRZuMtGhFXZbp4Bfk2zF3u2sG7Fp0Y9BWbYMZdHhVXhv1v-LMRq39i2JV2l5BU8DnU0Dwv3YYRzWY2KK12qHfRcWgrAUFmcDyCLbBxxiwf3uEgjoUpd6KUoeiFEh1KCoZr_794l_bqZkEfDkCG7Pe7E1AFQdtbcKp2u_3TCoqFJcp8w-RtZ6_</recordid><startdate>20080402</startdate><enddate>20080402</enddate><creator>Tysseling-Mattiace, Vicki M</creator><creator>Sahni, Vibhu</creator><creator>Niece, Krista L</creator><creator>Birch, Derin</creator><creator>Czeisler, Catherine</creator><creator>Fehlings, Michael G</creator><creator>Stupp, Samuel I</creator><creator>Kessler, John A</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</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>7TK</scope><scope>5PM</scope></search><sort><creationdate>20080402</creationdate><title>Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury</title><author>Tysseling-Mattiace, Vicki M ; Sahni, Vibhu ; Niece, Krista L ; Birch, Derin ; Czeisler, Catherine ; Fehlings, Michael G ; Stupp, Samuel I ; Kessler, John A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c594t-a134122e318a691a972540657e39730e950beadd31ef85eae4cc5915c4966c493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Axons - drug effects</topic><topic>Axons - physiology</topic><topic>Caspase 3 - metabolism</topic><topic>Cicatrix - drug therapy</topic><topic>Diagnostic Imaging - methods</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Glial Fibrillary Acidic Protein - metabolism</topic><topic>Gliosis - drug therapy</topic><topic>Laminin - metabolism</topic><topic>Laminin - therapeutic use</topic><topic>Mice</topic><topic>Motor Neurons - pathology</topic><topic>Nerve Regeneration - drug effects</topic><topic>Neuroglia - drug effects</topic><topic>Peptide Fragments - metabolism</topic><topic>Peptide Fragments - therapeutic use</topic><topic>Recovery of Function - drug effects</topic><topic>Spinal Cord Injuries - drug therapy</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tysseling-Mattiace, Vicki M</creatorcontrib><creatorcontrib>Sahni, Vibhu</creatorcontrib><creatorcontrib>Niece, Krista L</creatorcontrib><creatorcontrib>Birch, Derin</creatorcontrib><creatorcontrib>Czeisler, Catherine</creatorcontrib><creatorcontrib>Fehlings, Michael G</creatorcontrib><creatorcontrib>Stupp, Samuel I</creatorcontrib><creatorcontrib>Kessler, John 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>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tysseling-Mattiace, Vicki M</au><au>Sahni, Vibhu</au><au>Niece, Krista L</au><au>Birch, Derin</au><au>Czeisler, Catherine</au><au>Fehlings, Michael G</au><au>Stupp, Samuel I</au><au>Kessler, John A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2008-04-02</date><risdate>2008</risdate><volume>28</volume><issue>14</issue><spage>3814</spage><epage>3823</epage><pages>3814-3823</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><abstract>Peptide amphiphile (PA) molecules that self-assemble in vivo into supramolecular nanofibers were used as a therapy in a mouse model of spinal cord injury (SCI). Because self-assembly of these molecules is triggered by the ionic strength of the in vivo environment, nanoscale structures can be created within the extracellular spaces of the spinal cord by simply injecting a liquid. The molecules are designed to form cylindrical nanofibers that display to cells in the spinal cord the laminin epitope IKVAV at nearly van der Waals density. IKVAV PA nanofibers are known to inhibit glial differentiation of cultured neural stem cells and to promote neurite outgrowth from cultured neurons. In this work, in vivo treatment with the PA after SCI reduced astrogliosis, reduced cell death, and increased the number of oligodendroglia at the site of injury. Furthermore, the nanofibers promoted regeneration of both descending motor fibers and ascending sensory fibers through the lesion site. Treatment with the PA also resulted in significant behavioral improvement. These observations demonstrate that it is possible to inhibit glial scar formation and to facilitate regeneration after SCI using bioactive three-dimensional nanostructures displaying high densities of neuroactive epitopes on their surfaces.</abstract><cop>United States</cop><pub>Soc Neuroscience</pub><pmid>18385339</pmid><doi>10.1523/JNEUROSCI.0143-08.2008</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Analysis of Variance Animals Apoptosis - drug effects Axons - drug effects Axons - physiology Caspase 3 - metabolism Cicatrix - drug therapy Diagnostic Imaging - methods Disease Models, Animal Female Glial Fibrillary Acidic Protein - metabolism Gliosis - drug therapy Laminin - metabolism Laminin - therapeutic use Mice Motor Neurons - pathology Nerve Regeneration - drug effects Neuroglia - drug effects Peptide Fragments - metabolism Peptide Fragments - therapeutic use Recovery of Function - drug effects Spinal Cord Injuries - drug therapy Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology Time Factors |
title | Self-Assembling Nanofibers Inhibit Glial Scar Formation and Promote Axon Elongation after Spinal Cord Injury |
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