Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury
CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix depo...
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| Veröffentlicht in: | Cell 2018-03, Vol.173 (1), p.153-165.e22 |
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| creator | Dias, David Oliveira Kim, Hoseok Holl, Daniel Werne Solnestam, Beata Lundeberg, Joakim Carlén, Marie Göritz, Christian Frisén, Jonas |
| description | CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury.
[Display omitted]
•Inhibition of pericyte proliferation reduces fibrotic scar tissue following injury•Attenuated pericyte-derived scarring facilitates motor axon regeneration•Regenerated axons functionally re-integrate into the local spinal circuitry•Attenuated pericyte-derived scarring improves sensorimotor recovery
Attenuation of fibrotic tissue generation by a subset of pericytes promotes regeneration of serotonergic and corticospinal tract axons and improves functional recovery after spinal cord injury. |
| doi_str_mv | 10.1016/j.cell.2018.02.004 |
| format | Article |
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[Display omitted]
•Inhibition of pericyte proliferation reduces fibrotic scar tissue following injury•Attenuated pericyte-derived scarring facilitates motor axon regeneration•Regenerated axons functionally re-integrate into the local spinal circuitry•Attenuated pericyte-derived scarring improves sensorimotor recovery
Attenuation of fibrotic tissue generation by a subset of pericytes promotes regeneration of serotonergic and corticospinal tract axons and improves functional recovery after spinal cord injury.</description><identifier>ISSN: 0092-8674</identifier><identifier>ISSN: 1097-4172</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/j.cell.2018.02.004</identifier><identifier>PMID: 29502968</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; axon regeneration ; Axons - physiology ; Axons - radiation effects ; Cicatrix - pathology ; Disease Models, Animal ; Evoked Potentials - radiation effects ; Extracellular Matrix - metabolism ; Fibrosis ; Light ; Medicin och hälsovetenskap ; Mice ; Mice, Transgenic ; optogenetics ; pericyte ; Pericytes - cytology ; Pericytes - metabolism ; Photic Stimulation ; Pyramidal Tracts - physiology ; Receptor, Platelet-Derived Growth Factor beta - genetics ; Receptor, Platelet-Derived Growth Factor beta - metabolism ; Recovery of Function ; Regeneration ; scar ; Sensorimotor Cortex - physiology ; sensorimotor functional recovery ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - physiopathology ; spinal cord injury</subject><ispartof>Cell, 2018-03, Vol.173 (1), p.153-165.e22</ispartof><rights>2018 The Author(s)</rights><rights>Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.</rights><rights>2018 The Author(s) 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c543t-6b61bdf7bb92c10986e2eebcd5d88d55a31016b2e4e180f6f120d5d8127b7cd83</citedby><cites>FETCH-LOGICAL-c543t-6b61bdf7bb92c10986e2eebcd5d88d55a31016b2e4e180f6f120d5d8127b7cd83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cell.2018.02.004$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,552,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29502968$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:137864063$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Dias, David Oliveira</creatorcontrib><creatorcontrib>Kim, Hoseok</creatorcontrib><creatorcontrib>Holl, Daniel</creatorcontrib><creatorcontrib>Werne Solnestam, Beata</creatorcontrib><creatorcontrib>Lundeberg, Joakim</creatorcontrib><creatorcontrib>Carlén, Marie</creatorcontrib><creatorcontrib>Göritz, Christian</creatorcontrib><creatorcontrib>Frisén, Jonas</creatorcontrib><title>Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury</title><title>Cell</title><addtitle>Cell</addtitle><description>CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury.
[Display omitted]
•Inhibition of pericyte proliferation reduces fibrotic scar tissue following injury•Attenuated pericyte-derived scarring facilitates motor axon regeneration•Regenerated axons functionally re-integrate into the local spinal circuitry•Attenuated pericyte-derived scarring improves sensorimotor recovery
Attenuation of fibrotic tissue generation by a subset of pericytes promotes regeneration of serotonergic and corticospinal tract axons and improves functional recovery after spinal cord injury.</description><subject>Animals</subject><subject>axon regeneration</subject><subject>Axons - physiology</subject><subject>Axons - radiation effects</subject><subject>Cicatrix - pathology</subject><subject>Disease Models, Animal</subject><subject>Evoked Potentials - radiation effects</subject><subject>Extracellular Matrix - metabolism</subject><subject>Fibrosis</subject><subject>Light</subject><subject>Medicin och hälsovetenskap</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>optogenetics</subject><subject>pericyte</subject><subject>Pericytes - cytology</subject><subject>Pericytes - metabolism</subject><subject>Photic Stimulation</subject><subject>Pyramidal Tracts - physiology</subject><subject>Receptor, Platelet-Derived Growth Factor beta - genetics</subject><subject>Receptor, Platelet-Derived Growth Factor beta - metabolism</subject><subject>Recovery of Function</subject><subject>Regeneration</subject><subject>scar</subject><subject>Sensorimotor Cortex - physiology</subject><subject>sensorimotor functional recovery</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - physiopathology</subject><subject>spinal cord injury</subject><issn>0092-8674</issn><issn>1097-4172</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNp9kctu2zAQRYkiQeOk_YEuCv2AlCElPgQUBQLnCSRIYbdrQiJHKV1ZNCjZgf8-VJznollxwLnnDoeXkG8UMgpUHC8yg22bMaAqA5YBFJ_IhEIp04JKtkcmACVLlZDFATns-wUAKM75Z3LASg6sFGpCbmZo18Z1d8kvDM5sB0xPY7FBm8xNFcJjJ_ilH7BPZmj8BsM2qZoBQzJfua5qk6kPNrnqFuuw_UL2m6rt8evTeUT-nJ_9nl6m17cXV9OT69TwIh9SUQta20bWdclMfLASyBBrY7lVynJe5eN-NcMCqYJGNJTB2KNM1tJYlR-RdOfb3-NqXetVcMsqbLWvnH66-hcr1EUJwEXUl__Vr4K3r9AzSHOpRAEij-zPHRsFS7QGuyFU7XuLd53O_dV3fqO5klTSMhqwnYEJvu8DNi8sBT0uqhd6DFKPQWpgOgYZoe9vp74gz8lFwY-dAOM_bxwG3RuHnUHrAppBW-8-8n8A5QiyxQ</recordid><startdate>20180322</startdate><enddate>20180322</enddate><creator>Dias, David Oliveira</creator><creator>Kim, Hoseok</creator><creator>Holl, Daniel</creator><creator>Werne Solnestam, Beata</creator><creator>Lundeberg, Joakim</creator><creator>Carlén, Marie</creator><creator>Göritz, Christian</creator><creator>Frisén, Jonas</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><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>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20180322</creationdate><title>Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury</title><author>Dias, David Oliveira ; Kim, Hoseok ; Holl, Daniel ; Werne Solnestam, Beata ; Lundeberg, Joakim ; Carlén, Marie ; Göritz, Christian ; Frisén, Jonas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c543t-6b61bdf7bb92c10986e2eebcd5d88d55a31016b2e4e180f6f120d5d8127b7cd83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>axon regeneration</topic><topic>Axons - physiology</topic><topic>Axons - radiation effects</topic><topic>Cicatrix - pathology</topic><topic>Disease Models, Animal</topic><topic>Evoked Potentials - radiation effects</topic><topic>Extracellular Matrix - metabolism</topic><topic>Fibrosis</topic><topic>Light</topic><topic>Medicin och hälsovetenskap</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>optogenetics</topic><topic>pericyte</topic><topic>Pericytes - cytology</topic><topic>Pericytes - metabolism</topic><topic>Photic Stimulation</topic><topic>Pyramidal Tracts - physiology</topic><topic>Receptor, Platelet-Derived Growth Factor beta - genetics</topic><topic>Receptor, Platelet-Derived Growth Factor beta - metabolism</topic><topic>Recovery of Function</topic><topic>Regeneration</topic><topic>scar</topic><topic>Sensorimotor Cortex - physiology</topic><topic>sensorimotor functional recovery</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - physiopathology</topic><topic>spinal cord injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dias, David Oliveira</creatorcontrib><creatorcontrib>Kim, Hoseok</creatorcontrib><creatorcontrib>Holl, Daniel</creatorcontrib><creatorcontrib>Werne Solnestam, Beata</creatorcontrib><creatorcontrib>Lundeberg, Joakim</creatorcontrib><creatorcontrib>Carlén, Marie</creatorcontrib><creatorcontrib>Göritz, Christian</creatorcontrib><creatorcontrib>Frisén, Jonas</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dias, David Oliveira</au><au>Kim, Hoseok</au><au>Holl, Daniel</au><au>Werne Solnestam, Beata</au><au>Lundeberg, Joakim</au><au>Carlén, Marie</au><au>Göritz, Christian</au><au>Frisén, Jonas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2018-03-22</date><risdate>2018</risdate><volume>173</volume><issue>1</issue><spage>153</spage><epage>165.e22</epage><pages>153-165.e22</pages><issn>0092-8674</issn><issn>1097-4172</issn><eissn>1097-4172</eissn><abstract>CNS injury often severs axons. Scar tissue that forms locally at the lesion site is thought to block axonal regeneration, resulting in permanent functional deficits. We report that inhibiting the generation of progeny by a subclass of pericytes led to decreased fibrosis and extracellular matrix deposition after spinal cord injury in mice. Regeneration of raphespinal and corticospinal tract axons was enhanced and sensorimotor function recovery improved following spinal cord injury in animals with attenuated pericyte-derived scarring. Using optogenetic stimulation, we demonstrate that regenerated corticospinal tract axons integrated into the local spinal cord circuitry below the lesion site. The number of regenerated axons correlated with improved sensorimotor function recovery. In conclusion, attenuation of pericyte-derived fibrosis represents a promising therapeutic approach to facilitate recovery following CNS injury.
[Display omitted]
•Inhibition of pericyte proliferation reduces fibrotic scar tissue following injury•Attenuated pericyte-derived scarring facilitates motor axon regeneration•Regenerated axons functionally re-integrate into the local spinal circuitry•Attenuated pericyte-derived scarring improves sensorimotor recovery
Attenuation of fibrotic tissue generation by a subset of pericytes promotes regeneration of serotonergic and corticospinal tract axons and improves functional recovery after spinal cord injury.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>29502968</pmid><doi>10.1016/j.cell.2018.02.004</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals axon regeneration Axons - physiology Axons - radiation effects Cicatrix - pathology Disease Models, Animal Evoked Potentials - radiation effects Extracellular Matrix - metabolism Fibrosis Light Medicin och hälsovetenskap Mice Mice, Transgenic optogenetics pericyte Pericytes - cytology Pericytes - metabolism Photic Stimulation Pyramidal Tracts - physiology Receptor, Platelet-Derived Growth Factor beta - genetics Receptor, Platelet-Derived Growth Factor beta - metabolism Recovery of Function Regeneration scar Sensorimotor Cortex - physiology sensorimotor functional recovery Spinal Cord Injuries - pathology Spinal Cord Injuries - physiopathology spinal cord injury |
| title | Reducing Pericyte-Derived Scarring Promotes Recovery after Spinal Cord Injury |
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