Motor recovery and synaptic preservation after ventral root avulsion and repair with a fibrin sealant derived from snake venom
Ventral root avulsion is an experimental model of proximal axonal injury at the central/peripheral nervous system interface that results in paralysis and poor clinical outcome after restorative surgery. Root reimplantation may decrease neuronal degeneration in such cases. We describe the use of a sn...
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| creator | Barbizan, Roberta Castro, Mateus V Rodrigues, Antônio C Barraviera, Benedito Ferreira, Rui S Oliveira, Alexandre L R |
| description | Ventral root avulsion is an experimental model of proximal axonal injury at the central/peripheral nervous system interface that results in paralysis and poor clinical outcome after restorative surgery. Root reimplantation may decrease neuronal degeneration in such cases. We describe the use of a snake venom-derived fibrin sealant during surgical reconnection of avulsed roots at the spinal cord surface. The present work investigates the effects of this fibrin sealant on functional recovery, neuronal survival, synaptic plasticity, and glial reaction in the spinal motoneuron microenvironment after ventral root reimplantation.
Female Lewis rats (7 weeks old) were subjected to VRA and root replantation. The animals were divided into two groups: 1) avulsion only and 2) replanted roots with fibrin sealant derived from snake venom. Post-surgical motor performance was evaluated using the CatWalk system twice a week for 12 weeks. The rats were sacrificed 12 weeks after surgery, and their lumbar intumescences were processed for motoneuron counting and immunohistochemistry (GFAP, Iba-1 and synaptophysin antisera). Array based qRT-PCR was used to evaluate gene regulation of several neurotrophic factors and receptors as well as inflammatory related molecules. The results indicated that the root reimplantation with fibrin sealant enhanced motor recovery, preserved the synaptic covering of the motoneurons and improved neuronal survival. The replanted group did not show significant changes in microglial response compared to VRA-only. However, the astroglial reaction was significantly reduced in this group.
In conclusion, the present data suggest that the repair of avulsed roots with snake venom fibrin glue at the exact point of detachment results in neuroprotection and preservation of the synaptic network at the microenvironment of the lesioned motoneurons. Also such procedure reduced the astroglial reaction and increased mRNA levels to neurotrophins and anti-inflammatory cytokines that may in turn, contribute to improving recovery of motor function. |
| doi_str_mv | 10.1371/journal.pone.0063260 |
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Female Lewis rats (7 weeks old) were subjected to VRA and root replantation. The animals were divided into two groups: 1) avulsion only and 2) replanted roots with fibrin sealant derived from snake venom. Post-surgical motor performance was evaluated using the CatWalk system twice a week for 12 weeks. The rats were sacrificed 12 weeks after surgery, and their lumbar intumescences were processed for motoneuron counting and immunohistochemistry (GFAP, Iba-1 and synaptophysin antisera). Array based qRT-PCR was used to evaluate gene regulation of several neurotrophic factors and receptors as well as inflammatory related molecules. The results indicated that the root reimplantation with fibrin sealant enhanced motor recovery, preserved the synaptic covering of the motoneurons and improved neuronal survival. The replanted group did not show significant changes in microglial response compared to VRA-only. However, the astroglial reaction was significantly reduced in this group.
In conclusion, the present data suggest that the repair of avulsed roots with snake venom fibrin glue at the exact point of detachment results in neuroprotection and preservation of the synaptic network at the microenvironment of the lesioned motoneurons. Also such procedure reduced the astroglial reaction and increased mRNA levels to neurotrophins and anti-inflammatory cytokines that may in turn, contribute to improving recovery of motor function.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0063260</identifier><identifier>PMID: 23667596</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Antisera ; Apoptosis ; Biology ; Calcium-Binding Proteins - metabolism ; Cell survival ; Cytokines ; Degeneration ; Down-Regulation - drug effects ; Female ; Fibrin ; Fibrin Tissue Adhesive - pharmacology ; Fibrin Tissue Adhesive - therapeutic use ; Functional plasticity ; Gene expression ; Gene regulation ; Glial fibrillary acidic protein ; Glial Fibrillary Acidic Protein - metabolism ; Glial plasticity ; Immunohistochemistry ; Inflammation ; Ischemia ; Laboratories ; Microfilament Proteins - metabolism ; Motor neurons ; Motor Neurons - drug effects ; Motor Neurons - pathology ; Motor task performance ; mRNA ; Nerve Growth Factors - biosynthesis ; Nerve Regeneration - drug effects ; Nervous system ; Neuroglia - drug effects ; Neuroglia - metabolism ; Neuroglia - pathology ; Neuronal-glial interactions ; Neuroprotection ; Neuroprotective Agents - pharmacology ; Neurotrophic factors ; Paralysis ; Patient outcomes ; Peripheral nervous system ; Preservation ; Pressure ; Prosthesis Implantation ; Radiculopathy - drug therapy ; Radiculopathy - physiopathology ; Rats ; Rats, Inbred Lew ; Receptors ; Recovery ; Recovery (Medical) ; Recovery of function ; Recovery of Function - drug effects ; Repair ; Rodents ; Sealing compounds ; Snake Venoms - chemistry ; Spinal cord ; Spinal Cord - drug effects ; Spinal Cord - pathology ; Spinal Cord - physiopathology ; Spinal Nerve Roots - drug effects ; Spinal Nerve Roots - pathology ; Spinal Nerve Roots - physiopathology ; Studies ; Surgery ; Survival ; Synapses - drug effects ; Synapses - pathology ; Synaptophysin - metabolism ; Transplants & implants ; Trauma ; Up-Regulation - drug effects ; Venom ; Venoms ; Ventral roots ; Wound Healing - drug effects</subject><ispartof>PloS one, 2013-05, Vol.8 (5), p.e63260</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Barbizan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Barbizan et al 2013 Barbizan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e4cefc96bd38cf5458abd09d43545e0e02bc244acd677abec2119a74e51dc3833</citedby><cites>FETCH-LOGICAL-c692t-e4cefc96bd38cf5458abd09d43545e0e02bc244acd677abec2119a74e51dc3833</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/PMC3646764/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646764/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23667596$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Barbizan, Roberta</creatorcontrib><creatorcontrib>Castro, Mateus V</creatorcontrib><creatorcontrib>Rodrigues, Antônio C</creatorcontrib><creatorcontrib>Barraviera, Benedito</creatorcontrib><creatorcontrib>Ferreira, Rui S</creatorcontrib><creatorcontrib>Oliveira, Alexandre L R</creatorcontrib><title>Motor recovery and synaptic preservation after ventral root avulsion and repair with a fibrin sealant derived from snake venom</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Ventral root avulsion is an experimental model of proximal axonal injury at the central/peripheral nervous system interface that results in paralysis and poor clinical outcome after restorative surgery. Root reimplantation may decrease neuronal degeneration in such cases. We describe the use of a snake venom-derived fibrin sealant during surgical reconnection of avulsed roots at the spinal cord surface. The present work investigates the effects of this fibrin sealant on functional recovery, neuronal survival, synaptic plasticity, and glial reaction in the spinal motoneuron microenvironment after ventral root reimplantation.
Female Lewis rats (7 weeks old) were subjected to VRA and root replantation. The animals were divided into two groups: 1) avulsion only and 2) replanted roots with fibrin sealant derived from snake venom. Post-surgical motor performance was evaluated using the CatWalk system twice a week for 12 weeks. The rats were sacrificed 12 weeks after surgery, and their lumbar intumescences were processed for motoneuron counting and immunohistochemistry (GFAP, Iba-1 and synaptophysin antisera). Array based qRT-PCR was used to evaluate gene regulation of several neurotrophic factors and receptors as well as inflammatory related molecules. The results indicated that the root reimplantation with fibrin sealant enhanced motor recovery, preserved the synaptic covering of the motoneurons and improved neuronal survival. The replanted group did not show significant changes in microglial response compared to VRA-only. However, the astroglial reaction was significantly reduced in this group.
In conclusion, the present data suggest that the repair of avulsed roots with snake venom fibrin glue at the exact point of detachment results in neuroprotection and preservation of the synaptic network at the microenvironment of the lesioned motoneurons. Also such procedure reduced the astroglial reaction and increased mRNA levels to neurotrophins and anti-inflammatory cytokines that may in turn, contribute to improving recovery of motor function.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antisera</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Cell survival</subject><subject>Cytokines</subject><subject>Degeneration</subject><subject>Down-Regulation - drug effects</subject><subject>Female</subject><subject>Fibrin</subject><subject>Fibrin Tissue Adhesive - pharmacology</subject><subject>Fibrin Tissue Adhesive - therapeutic use</subject><subject>Functional plasticity</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Glial fibrillary acidic protein</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Glial plasticity</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Ischemia</subject><subject>Laboratories</subject><subject>Microfilament Proteins - metabolism</subject><subject>Motor neurons</subject><subject>Motor Neurons - drug effects</subject><subject>Motor Neurons - pathology</subject><subject>Motor task performance</subject><subject>mRNA</subject><subject>Nerve Growth Factors - biosynthesis</subject><subject>Nerve Regeneration - drug effects</subject><subject>Nervous system</subject><subject>Neuroglia - drug effects</subject><subject>Neuroglia - metabolism</subject><subject>Neuroglia - pathology</subject><subject>Neuronal-glial interactions</subject><subject>Neuroprotection</subject><subject>Neuroprotective Agents - pharmacology</subject><subject>Neurotrophic factors</subject><subject>Paralysis</subject><subject>Patient outcomes</subject><subject>Peripheral nervous system</subject><subject>Preservation</subject><subject>Pressure</subject><subject>Prosthesis Implantation</subject><subject>Radiculopathy - drug therapy</subject><subject>Radiculopathy - physiopathology</subject><subject>Rats</subject><subject>Rats, Inbred Lew</subject><subject>Receptors</subject><subject>Recovery</subject><subject>Recovery (Medical)</subject><subject>Recovery of function</subject><subject>Recovery of Function - drug effects</subject><subject>Repair</subject><subject>Rodents</subject><subject>Sealing compounds</subject><subject>Snake Venoms - chemistry</subject><subject>Spinal cord</subject><subject>Spinal Cord - drug effects</subject><subject>Spinal Cord - pathology</subject><subject>Spinal Cord - physiopathology</subject><subject>Spinal Nerve Roots - drug effects</subject><subject>Spinal Nerve Roots - pathology</subject><subject>Spinal Nerve Roots - physiopathology</subject><subject>Studies</subject><subject>Surgery</subject><subject>Survival</subject><subject>Synapses - drug effects</subject><subject>Synapses - pathology</subject><subject>Synaptophysin - metabolism</subject><subject>Transplants & implants</subject><subject>Trauma</subject><subject>Up-Regulation - drug effects</subject><subject>Venom</subject><subject>Venoms</subject><subject>Ventral roots</subject><subject>Wound Healing - drug effects</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAYhYso7rr6D0QDguDFjEmTpu2NsCx-DKws-HUb0uTNTNZOU5O0Ojf-djM73WUKCpKLhDfPOQmHk2VPCV4SWpLX127wnWyXvetgiTGnOcf3slNS03zBc0zvH51PskchXGNc0Irzh9lJTjkvi5qfZr8_uug88qDcCH6HZKdR2HWyj1ah3kMAP8poXYekieDRCF30skXeuYjkOLTh5i6pPPTSevTTxg2SyNjG2w4FkK3sItLg7QgaGe-2KHTyO-yd3PZx9sDINsCTaT_Lvr57--Xiw-Ly6v3q4vxyoXidxwUwBUbVvNG0UqZgRSUbjWvNaDoDBpw3KmdMKs3LUjagckJqWTIoiFa0ovQse37w7VsXxBRdEIQWuOZVgffE6kBoJ69F7-1W-p1w0oqbgfNrIX0KpQVRmIY2UBWmZoQ1mtR5zkpWkKZhlTGmSF5vpteGZgtaHTKbmc5vOrsRazcKyhkvOUsGLyYD734MEOI_vjxRa5l-ZTvjkpna2qDEOSsrWtOyyBO1_AuVloatVak8xqb5TPBqJkhMhF9xLYcQxOrzp_9nr77N2ZdH7CY1I26Ca4d9u8IcZAdQeReCB3OXHMFi3_3bNMS--2LqfpI9O079TnRbdvoHUccCLA</recordid><startdate>20130507</startdate><enddate>20130507</enddate><creator>Barbizan, Roberta</creator><creator>Castro, Mateus V</creator><creator>Rodrigues, Antônio C</creator><creator>Barraviera, Benedito</creator><creator>Ferreira, Rui S</creator><creator>Oliveira, Alexandre L R</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130507</creationdate><title>Motor recovery and synaptic preservation after ventral root avulsion and repair with a fibrin sealant derived from snake venom</title><author>Barbizan, Roberta ; Castro, Mateus V ; Rodrigues, Antônio C ; Barraviera, Benedito ; Ferreira, Rui S ; Oliveira, Alexandre L R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-e4cefc96bd38cf5458abd09d43545e0e02bc244acd677abec2119a74e51dc3833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Antisera</topic><topic>Apoptosis</topic><topic>Biology</topic><topic>Calcium-Binding Proteins - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barbizan, Roberta</au><au>Castro, Mateus V</au><au>Rodrigues, Antônio C</au><au>Barraviera, Benedito</au><au>Ferreira, Rui S</au><au>Oliveira, Alexandre L R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Motor recovery and synaptic preservation after ventral root avulsion and repair with a fibrin sealant derived from snake venom</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-05-07</date><risdate>2013</risdate><volume>8</volume><issue>5</issue><spage>e63260</spage><pages>e63260-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Ventral root avulsion is an experimental model of proximal axonal injury at the central/peripheral nervous system interface that results in paralysis and poor clinical outcome after restorative surgery. Root reimplantation may decrease neuronal degeneration in such cases. We describe the use of a snake venom-derived fibrin sealant during surgical reconnection of avulsed roots at the spinal cord surface. The present work investigates the effects of this fibrin sealant on functional recovery, neuronal survival, synaptic plasticity, and glial reaction in the spinal motoneuron microenvironment after ventral root reimplantation.
Female Lewis rats (7 weeks old) were subjected to VRA and root replantation. The animals were divided into two groups: 1) avulsion only and 2) replanted roots with fibrin sealant derived from snake venom. Post-surgical motor performance was evaluated using the CatWalk system twice a week for 12 weeks. The rats were sacrificed 12 weeks after surgery, and their lumbar intumescences were processed for motoneuron counting and immunohistochemistry (GFAP, Iba-1 and synaptophysin antisera). Array based qRT-PCR was used to evaluate gene regulation of several neurotrophic factors and receptors as well as inflammatory related molecules. The results indicated that the root reimplantation with fibrin sealant enhanced motor recovery, preserved the synaptic covering of the motoneurons and improved neuronal survival. The replanted group did not show significant changes in microglial response compared to VRA-only. However, the astroglial reaction was significantly reduced in this group.
In conclusion, the present data suggest that the repair of avulsed roots with snake venom fibrin glue at the exact point of detachment results in neuroprotection and preservation of the synaptic network at the microenvironment of the lesioned motoneurons. Also such procedure reduced the astroglial reaction and increased mRNA levels to neurotrophins and anti-inflammatory cytokines that may in turn, contribute to improving recovery of motor function.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23667596</pmid><doi>10.1371/journal.pone.0063260</doi><tpages>e63260</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-05, Vol.8 (5), p.e63260 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1350968503 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Animals Antisera Apoptosis Biology Calcium-Binding Proteins - metabolism Cell survival Cytokines Degeneration Down-Regulation - drug effects Female Fibrin Fibrin Tissue Adhesive - pharmacology Fibrin Tissue Adhesive - therapeutic use Functional plasticity Gene expression Gene regulation Glial fibrillary acidic protein Glial Fibrillary Acidic Protein - metabolism Glial plasticity Immunohistochemistry Inflammation Ischemia Laboratories Microfilament Proteins - metabolism Motor neurons Motor Neurons - drug effects Motor Neurons - pathology Motor task performance mRNA Nerve Growth Factors - biosynthesis Nerve Regeneration - drug effects Nervous system Neuroglia - drug effects Neuroglia - metabolism Neuroglia - pathology Neuronal-glial interactions Neuroprotection Neuroprotective Agents - pharmacology Neurotrophic factors Paralysis Patient outcomes Peripheral nervous system Preservation Pressure Prosthesis Implantation Radiculopathy - drug therapy Radiculopathy - physiopathology Rats Rats, Inbred Lew Receptors Recovery Recovery (Medical) Recovery of function Recovery of Function - drug effects Repair Rodents Sealing compounds Snake Venoms - chemistry Spinal cord Spinal Cord - drug effects Spinal Cord - pathology Spinal Cord - physiopathology Spinal Nerve Roots - drug effects Spinal Nerve Roots - pathology Spinal Nerve Roots - physiopathology Studies Surgery Survival Synapses - drug effects Synapses - pathology Synaptophysin - metabolism Transplants & implants Trauma Up-Regulation - drug effects Venom Venoms Ventral roots Wound Healing - drug effects |
| title | Motor recovery and synaptic preservation after ventral root avulsion and repair with a fibrin sealant derived from snake venom |
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