Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury
To assess the therapeutic effects of microRNA-21 (miR-21) knockdown (KD) for acute thoracic spinal cord contusion using a mouse model. Forty C57/BL6 mice were randomly divided into four groups: mice in the sham-operated (Sham) group received surgical procedure without spinal cord contusion; the spin...
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| creator | Xie, Wei Yang, Shang-you Zhang, Qianqian Zhou, Yadong Wang, Yi Liu, Ronghan Wang, Wenzhao Shi, Jixue Ning, Bin Jia, Tanghong |
| description | To assess the therapeutic effects of microRNA-21 (miR-21) knockdown (KD) for acute thoracic spinal cord contusion using a mouse model. Forty C57/BL6 mice were randomly divided into four groups: mice in the sham-operated (Sham) group received surgical procedure without spinal cord contusion; the spinal cord injury (SCI) group mice underwent spinal cord contusion without treatment; mice in the miR-21 KD group underwent spinal cord contusion followed by a single dose subdural injection of miR-21 KD vectors (1 × 10
7
TU); and the negative control (NC) group mice were given subdural injection of comparable amount of NC vectors (1 × 10
7
TU) after spinal cord contusion. The Basso Mouse Scale (BMS) was employed to assess hindlimb motor functions. Hematoxylin–eosin and Luxol fast blue staining were performed to evaluate pathologic changes in spinal cord tissues. Peripheral blood serum levels of tumor necrosis factor α (TNFα), transforming growth factor β (TGF-β) and interleukin-1β (IL-1β) were determined by the enzyme-linked immunosorbent assay, and mRNA expression of Brain derived neurotrophic factor (BDNF) was examined by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was performed to analyze the AKT signaling pathway. KD of miRNA-21 effectively improved the BMS scores at day 14 post-surgery compared with the SCI group (
p
|
| doi_str_mv | 10.1007/s11064-018-2580-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2058506078</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2058108197</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-20067c4bd0080b14a57fdf80e6453fc40c513d1bb1107fef012afc8bcebe1b643</originalsourceid><addsrcrecordid>eNp1kEtP4zAUhS00CArDD5jNyNJs2ATutfNcVhUvUWDEa2slzjVKJ42LnYD673EVHtJIrLw43zm2P8Z-IRwhQHbsESGNI8A8EkkOEW6xCSaZjNIC5A82ARlSiQXssj3vFwChJXCH7YqikHGAJuzxsrP6X21fO24Nv2q0s7fX00gg_-vs0vbk-TUNzrb2qdFly29J2xdyaz41PTk-1UNP_G7VdCGbWVfzi24xuPVPtm3K1tPB-7nPHk5P7mfn0fzm7GI2nUdaZqKPBECa6biqAXKoMC6TzNQmB0rjRBodg05Q1lhV4aOZIQMoSqPzSlNFWKWx3GeH4-7K2eeBfK-WjdfUtmVHdvBKQJInkEKWB_TPf-jCDi68e6QQciyyQOFIBRHeOzJq5Zpl6dYKQW2kq1G6CtLVRrrC0Pn9vjxUS6o_Gx-WAyBGwIeoeyL3dfX3q2_1oYr1</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2058108197</pqid></control><display><type>article</type><title>Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Xie, Wei ; Yang, Shang-you ; Zhang, Qianqian ; Zhou, Yadong ; Wang, Yi ; Liu, Ronghan ; Wang, Wenzhao ; Shi, Jixue ; Ning, Bin ; Jia, Tanghong</creator><creatorcontrib>Xie, Wei ; Yang, Shang-you ; Zhang, Qianqian ; Zhou, Yadong ; Wang, Yi ; Liu, Ronghan ; Wang, Wenzhao ; Shi, Jixue ; Ning, Bin ; Jia, Tanghong</creatorcontrib><description>To assess the therapeutic effects of microRNA-21 (miR-21) knockdown (KD) for acute thoracic spinal cord contusion using a mouse model. Forty C57/BL6 mice were randomly divided into four groups: mice in the sham-operated (Sham) group received surgical procedure without spinal cord contusion; the spinal cord injury (SCI) group mice underwent spinal cord contusion without treatment; mice in the miR-21 KD group underwent spinal cord contusion followed by a single dose subdural injection of miR-21 KD vectors (1 × 10
7
TU); and the negative control (NC) group mice were given subdural injection of comparable amount of NC vectors (1 × 10
7
TU) after spinal cord contusion. The Basso Mouse Scale (BMS) was employed to assess hindlimb motor functions. Hematoxylin–eosin and Luxol fast blue staining were performed to evaluate pathologic changes in spinal cord tissues. Peripheral blood serum levels of tumor necrosis factor α (TNFα), transforming growth factor β (TGF-β) and interleukin-1β (IL-1β) were determined by the enzyme-linked immunosorbent assay, and mRNA expression of Brain derived neurotrophic factor (BDNF) was examined by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was performed to analyze the AKT signaling pathway. KD of miRNA-21 effectively improved the BMS scores at day 14 post-surgery compared with the SCI group (
p
< 0.01). The spinal cord tissue in the miR-21 KD group displayed the most overt histologic signs of recovery, with axonal regeneration and the recovery of neuronal morphology at day 14 post-surgery. Significantly alleviation of TGF-β1, TNF-α and IL-1β was also found in sera from the miR-21 inhibition group in comparison to others, whereas BDNF gene expression was upregulated following miR-21 KD (
p
< 0.01). Further, significantly decreased AKT phosphorylation activity was illustrated in the miR-21 KD group (
p
< 0.001). The data suggest that miR-21 KD significantly reduces the inflammatory response at the damaged spinal cord site and promotes motor functional recovery. The treatment also elevated expression of BDNF, a neurotrophin participating in nerve regeneration.</description><identifier>ISSN: 0364-3190</identifier><identifier>EISSN: 1573-6903</identifier><identifier>DOI: 10.1007/s11064-018-2580-1</identifier><identifier>PMID: 29934690</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>AKT protein ; Animals ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Brain ; Brain-derived neurotrophic factor ; Brain-Derived Neurotrophic Factor - genetics ; Cell Biology ; Cytokines - metabolism ; Enzyme-linked immunosorbent assay ; Female ; Gene expression ; Gene Expression Regulation - genetics ; Gene Knockdown Techniques ; Genetic Therapy - methods ; IL-1β ; Inflammation ; Inflammatory response ; Injection ; Interleukins ; Mice ; Mice, Inbred C57BL ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Morphology ; Nerve Regeneration - genetics ; Neurochemistry ; Neurology ; Neurosciences ; Original Paper ; Peripheral blood ; Phosphorylation ; Polymerase chain reaction ; Proto-Oncogene Proteins c-akt - metabolism ; Recovery ; Recovery of function ; Regeneration ; Reverse transcription ; Ribonucleic acid ; RNA ; RNA, Messenger - genetics ; Serum levels ; Signal transduction ; Signal Transduction - physiology ; Spinal Cord - pathology ; Spinal cord injuries ; Spinal Cord Injuries - pathology ; Spinal Cord Injuries - therapy ; Surgery ; Thorax ; Transforming growth factor ; Transforming growth factor-b ; Transforming growth factor-b1 ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Western blotting</subject><ispartof>Neurochemical research, 2018-08, Vol.43 (8), p.1641-1649</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2018</rights><rights>Neurochemical Research is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-20067c4bd0080b14a57fdf80e6453fc40c513d1bb1107fef012afc8bcebe1b643</citedby><cites>FETCH-LOGICAL-c372t-20067c4bd0080b14a57fdf80e6453fc40c513d1bb1107fef012afc8bcebe1b643</cites><orcidid>0000-0002-7592-9485</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11064-018-2580-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11064-018-2580-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29934690$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xie, Wei</creatorcontrib><creatorcontrib>Yang, Shang-you</creatorcontrib><creatorcontrib>Zhang, Qianqian</creatorcontrib><creatorcontrib>Zhou, Yadong</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Liu, Ronghan</creatorcontrib><creatorcontrib>Wang, Wenzhao</creatorcontrib><creatorcontrib>Shi, Jixue</creatorcontrib><creatorcontrib>Ning, Bin</creatorcontrib><creatorcontrib>Jia, Tanghong</creatorcontrib><title>Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury</title><title>Neurochemical research</title><addtitle>Neurochem Res</addtitle><addtitle>Neurochem Res</addtitle><description>To assess the therapeutic effects of microRNA-21 (miR-21) knockdown (KD) for acute thoracic spinal cord contusion using a mouse model. Forty C57/BL6 mice were randomly divided into four groups: mice in the sham-operated (Sham) group received surgical procedure without spinal cord contusion; the spinal cord injury (SCI) group mice underwent spinal cord contusion without treatment; mice in the miR-21 KD group underwent spinal cord contusion followed by a single dose subdural injection of miR-21 KD vectors (1 × 10
7
TU); and the negative control (NC) group mice were given subdural injection of comparable amount of NC vectors (1 × 10
7
TU) after spinal cord contusion. The Basso Mouse Scale (BMS) was employed to assess hindlimb motor functions. Hematoxylin–eosin and Luxol fast blue staining were performed to evaluate pathologic changes in spinal cord tissues. Peripheral blood serum levels of tumor necrosis factor α (TNFα), transforming growth factor β (TGF-β) and interleukin-1β (IL-1β) were determined by the enzyme-linked immunosorbent assay, and mRNA expression of Brain derived neurotrophic factor (BDNF) was examined by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was performed to analyze the AKT signaling pathway. KD of miRNA-21 effectively improved the BMS scores at day 14 post-surgery compared with the SCI group (
p
< 0.01). The spinal cord tissue in the miR-21 KD group displayed the most overt histologic signs of recovery, with axonal regeneration and the recovery of neuronal morphology at day 14 post-surgery. Significantly alleviation of TGF-β1, TNF-α and IL-1β was also found in sera from the miR-21 inhibition group in comparison to others, whereas BDNF gene expression was upregulated following miR-21 KD (
p
< 0.01). Further, significantly decreased AKT phosphorylation activity was illustrated in the miR-21 KD group (
p
< 0.001). The data suggest that miR-21 KD significantly reduces the inflammatory response at the damaged spinal cord site and promotes motor functional recovery. The treatment also elevated expression of BDNF, a neurotrophin participating in nerve regeneration.</description><subject>AKT protein</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain</subject><subject>Brain-derived neurotrophic factor</subject><subject>Brain-Derived Neurotrophic Factor - genetics</subject><subject>Cell Biology</subject><subject>Cytokines - metabolism</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - genetics</subject><subject>Gene Knockdown Techniques</subject><subject>Genetic Therapy - methods</subject><subject>IL-1β</subject><subject>Inflammation</subject><subject>Inflammatory response</subject><subject>Injection</subject><subject>Interleukins</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>miRNA</subject><subject>Morphology</subject><subject>Nerve Regeneration - genetics</subject><subject>Neurochemistry</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Original Paper</subject><subject>Peripheral blood</subject><subject>Phosphorylation</subject><subject>Polymerase chain reaction</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Recovery</subject><subject>Recovery of function</subject><subject>Regeneration</subject><subject>Reverse transcription</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger - genetics</subject><subject>Serum levels</subject><subject>Signal transduction</subject><subject>Signal Transduction - physiology</subject><subject>Spinal Cord - pathology</subject><subject>Spinal cord injuries</subject><subject>Spinal Cord Injuries - pathology</subject><subject>Spinal Cord Injuries - therapy</subject><subject>Surgery</subject><subject>Thorax</subject><subject>Transforming growth factor</subject><subject>Transforming growth factor-b</subject><subject>Transforming growth factor-b1</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Western blotting</subject><issn>0364-3190</issn><issn>1573-6903</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kEtP4zAUhS00CArDD5jNyNJs2ATutfNcVhUvUWDEa2slzjVKJ42LnYD673EVHtJIrLw43zm2P8Z-IRwhQHbsESGNI8A8EkkOEW6xCSaZjNIC5A82ARlSiQXssj3vFwChJXCH7YqikHGAJuzxsrP6X21fO24Nv2q0s7fX00gg_-vs0vbk-TUNzrb2qdFly29J2xdyaz41PTk-1UNP_G7VdCGbWVfzi24xuPVPtm3K1tPB-7nPHk5P7mfn0fzm7GI2nUdaZqKPBECa6biqAXKoMC6TzNQmB0rjRBodg05Q1lhV4aOZIQMoSqPzSlNFWKWx3GeH4-7K2eeBfK-WjdfUtmVHdvBKQJInkEKWB_TPf-jCDi68e6QQciyyQOFIBRHeOzJq5Zpl6dYKQW2kq1G6CtLVRrrC0Pn9vjxUS6o_Gx-WAyBGwIeoeyL3dfX3q2_1oYr1</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Xie, Wei</creator><creator>Yang, Shang-you</creator><creator>Zhang, Qianqian</creator><creator>Zhou, Yadong</creator><creator>Wang, Yi</creator><creator>Liu, Ronghan</creator><creator>Wang, Wenzhao</creator><creator>Shi, Jixue</creator><creator>Ning, Bin</creator><creator>Jia, Tanghong</creator><general>Springer US</general><general>Springer Nature B.V</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>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7592-9485</orcidid></search><sort><creationdate>20180801</creationdate><title>Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury</title><author>Xie, Wei ; Yang, Shang-you ; Zhang, Qianqian ; Zhou, Yadong ; Wang, Yi ; Liu, Ronghan ; Wang, Wenzhao ; Shi, Jixue ; Ning, Bin ; Jia, Tanghong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-20067c4bd0080b14a57fdf80e6453fc40c513d1bb1107fef012afc8bcebe1b643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>AKT protein</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain</topic><topic>Brain-derived neurotrophic factor</topic><topic>Brain-Derived Neurotrophic Factor - genetics</topic><topic>Cell Biology</topic><topic>Cytokines - metabolism</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - genetics</topic><topic>Gene Knockdown Techniques</topic><topic>Genetic Therapy - methods</topic><topic>IL-1β</topic><topic>Inflammation</topic><topic>Inflammatory response</topic><topic>Injection</topic><topic>Interleukins</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>Morphology</topic><topic>Nerve Regeneration - genetics</topic><topic>Neurochemistry</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Original Paper</topic><topic>Peripheral blood</topic><topic>Phosphorylation</topic><topic>Polymerase chain reaction</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Recovery</topic><topic>Recovery of function</topic><topic>Regeneration</topic><topic>Reverse transcription</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Messenger - genetics</topic><topic>Serum levels</topic><topic>Signal transduction</topic><topic>Signal Transduction - physiology</topic><topic>Spinal Cord - pathology</topic><topic>Spinal cord injuries</topic><topic>Spinal Cord Injuries - pathology</topic><topic>Spinal Cord Injuries - therapy</topic><topic>Surgery</topic><topic>Thorax</topic><topic>Transforming growth factor</topic><topic>Transforming growth factor-b</topic><topic>Transforming growth factor-b1</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xie, Wei</creatorcontrib><creatorcontrib>Yang, Shang-you</creatorcontrib><creatorcontrib>Zhang, Qianqian</creatorcontrib><creatorcontrib>Zhou, Yadong</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Liu, Ronghan</creatorcontrib><creatorcontrib>Wang, Wenzhao</creatorcontrib><creatorcontrib>Shi, Jixue</creatorcontrib><creatorcontrib>Ning, Bin</creatorcontrib><creatorcontrib>Jia, Tanghong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>MEDLINE - Academic</collection><jtitle>Neurochemical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xie, Wei</au><au>Yang, Shang-you</au><au>Zhang, Qianqian</au><au>Zhou, Yadong</au><au>Wang, Yi</au><au>Liu, Ronghan</au><au>Wang, Wenzhao</au><au>Shi, Jixue</au><au>Ning, Bin</au><au>Jia, Tanghong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury</atitle><jtitle>Neurochemical research</jtitle><stitle>Neurochem Res</stitle><addtitle>Neurochem Res</addtitle><date>2018-08-01</date><risdate>2018</risdate><volume>43</volume><issue>8</issue><spage>1641</spage><epage>1649</epage><pages>1641-1649</pages><issn>0364-3190</issn><eissn>1573-6903</eissn><abstract>To assess the therapeutic effects of microRNA-21 (miR-21) knockdown (KD) for acute thoracic spinal cord contusion using a mouse model. Forty C57/BL6 mice were randomly divided into four groups: mice in the sham-operated (Sham) group received surgical procedure without spinal cord contusion; the spinal cord injury (SCI) group mice underwent spinal cord contusion without treatment; mice in the miR-21 KD group underwent spinal cord contusion followed by a single dose subdural injection of miR-21 KD vectors (1 × 10
7
TU); and the negative control (NC) group mice were given subdural injection of comparable amount of NC vectors (1 × 10
7
TU) after spinal cord contusion. The Basso Mouse Scale (BMS) was employed to assess hindlimb motor functions. Hematoxylin–eosin and Luxol fast blue staining were performed to evaluate pathologic changes in spinal cord tissues. Peripheral blood serum levels of tumor necrosis factor α (TNFα), transforming growth factor β (TGF-β) and interleukin-1β (IL-1β) were determined by the enzyme-linked immunosorbent assay, and mRNA expression of Brain derived neurotrophic factor (BDNF) was examined by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was performed to analyze the AKT signaling pathway. KD of miRNA-21 effectively improved the BMS scores at day 14 post-surgery compared with the SCI group (
p
< 0.01). The spinal cord tissue in the miR-21 KD group displayed the most overt histologic signs of recovery, with axonal regeneration and the recovery of neuronal morphology at day 14 post-surgery. Significantly alleviation of TGF-β1, TNF-α and IL-1β was also found in sera from the miR-21 inhibition group in comparison to others, whereas BDNF gene expression was upregulated following miR-21 KD (
p
< 0.01). Further, significantly decreased AKT phosphorylation activity was illustrated in the miR-21 KD group (
p
< 0.001). The data suggest that miR-21 KD significantly reduces the inflammatory response at the damaged spinal cord site and promotes motor functional recovery. The treatment also elevated expression of BDNF, a neurotrophin participating in nerve regeneration.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>29934690</pmid><doi>10.1007/s11064-018-2580-1</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7592-9485</orcidid></addata></record> |
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| subjects | AKT protein Animals Biochemistry Biomedical and Life Sciences Biomedicine Brain Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor - genetics Cell Biology Cytokines - metabolism Enzyme-linked immunosorbent assay Female Gene expression Gene Expression Regulation - genetics Gene Knockdown Techniques Genetic Therapy - methods IL-1β Inflammation Inflammatory response Injection Interleukins Mice Mice, Inbred C57BL MicroRNAs MicroRNAs - genetics miRNA Morphology Nerve Regeneration - genetics Neurochemistry Neurology Neurosciences Original Paper Peripheral blood Phosphorylation Polymerase chain reaction Proto-Oncogene Proteins c-akt - metabolism Recovery Recovery of function Regeneration Reverse transcription Ribonucleic acid RNA RNA, Messenger - genetics Serum levels Signal transduction Signal Transduction - physiology Spinal Cord - pathology Spinal cord injuries Spinal Cord Injuries - pathology Spinal Cord Injuries - therapy Surgery Thorax Transforming growth factor Transforming growth factor-b Transforming growth factor-b1 Tumor necrosis factor-TNF Tumor necrosis factor-α Western blotting |
| title | Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury |
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