Resolvin D3 Promotes Inflammatory Resolution, Neuroprotection, and Functional Recovery After Spinal Cord Injury
Resolvins, a new family from the endogenous specialized pro-resolving mediators (SPMs), promote the resolution of the inflammatory response. Resolvin D3 (RvD3), a docosahexaenoic acid (DHA) product, has been known to suppress the inflammatory response. However, the anti-inflammatory and neuroprotect...
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| Veröffentlicht in: | Molecular neurobiology 2021, Vol.58 (1), p.424-438 |
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| creator | Kim, Juri Joshi, Hari Prasad Sheen, Seung Hun Kim, Kyoung-Tae Kyung, Jae Won Choi, Hyemin Kim, Ye Won Kwon, Su Yeon Roh, Eun Ji Choi, Un Yong Sohn, Seil Kim, Yong Ho Park, Chul-Kyu Kumar, Hemant Han, In-Bo |
| description | Resolvins, a new family from the endogenous specialized pro-resolving mediators (SPMs), promote the resolution of the inflammatory response. Resolvin D3 (RvD3), a docosahexaenoic acid (DHA) product, has been known to suppress the inflammatory response. However, the anti-inflammatory and neuroprotective effects of RvD3 are not known in a model of spinal cord injury (SCI). Here, we investigated the anti-inflammatory and neuroprotective effect of RvD3 in a mouse model of SCI. Processes associated with anti-inflammation and angiogenesis were studied in RAW 264.7 cells and the human brain endothelial cell line hCMEC/D3, respectively. Additionally, female C57BL/6 mice were subjected to moderate compression SCI (20-g weight compression for 1 min) followed by intrathecal injection of vehicle or RvD3 (1 μg/20 μL) at 1 h post-SCI. RvD3 decreased the lipopolysaccharide (LPS)-induced production of inflammatory mediators and nitric oxide (NO) in RAW 264.7 cells and promoted an angiogenic effect in the hCMEC/D3 cell line. Treatment with RvD3 improved locomotor recovery and reduced thermal hyperalgesia in SCI mice compared with vehicle treatment at 14 days post-SCI. Remarkably, RvD3-treated mice exhibited reduced expression of inflammatory cytokines (TNF-α, IL6, IL1β) and chemokines (CCL2, CCL3). Also, RvD3-treated mice exhibited increased expression of tight junction proteins such as zonula occludens (ZO)-1 and occludin. Furthermore, immunohistochemistry showed a decreased level of gliosis (GFAP, Iba-1) and neuroinflammation (CD68, TGF-β) and enhanced neuroprotection. These data provide evidence that intrathecal injection of RvD3 represents a promising therapeutic strategy to promote inflammatory resolution, neuroprotection, and neurological functional recovery following SCI. |
| doi_str_mv | 10.1007/s12035-020-02118-7 |
| format | Article |
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Resolvin D3 (RvD3), a docosahexaenoic acid (DHA) product, has been known to suppress the inflammatory response. However, the anti-inflammatory and neuroprotective effects of RvD3 are not known in a model of spinal cord injury (SCI). Here, we investigated the anti-inflammatory and neuroprotective effect of RvD3 in a mouse model of SCI. Processes associated with anti-inflammation and angiogenesis were studied in RAW 264.7 cells and the human brain endothelial cell line hCMEC/D3, respectively. Additionally, female C57BL/6 mice were subjected to moderate compression SCI (20-g weight compression for 1 min) followed by intrathecal injection of vehicle or RvD3 (1 μg/20 μL) at 1 h post-SCI. RvD3 decreased the lipopolysaccharide (LPS)-induced production of inflammatory mediators and nitric oxide (NO) in RAW 264.7 cells and promoted an angiogenic effect in the hCMEC/D3 cell line. Treatment with RvD3 improved locomotor recovery and reduced thermal hyperalgesia in SCI mice compared with vehicle treatment at 14 days post-SCI. Remarkably, RvD3-treated mice exhibited reduced expression of inflammatory cytokines (TNF-α, IL6, IL1β) and chemokines (CCL2, CCL3). Also, RvD3-treated mice exhibited increased expression of tight junction proteins such as zonula occludens (ZO)-1 and occludin. Furthermore, immunohistochemistry showed a decreased level of gliosis (GFAP, Iba-1) and neuroinflammation (CD68, TGF-β) and enhanced neuroprotection. These data provide evidence that intrathecal injection of RvD3 represents a promising therapeutic strategy to promote inflammatory resolution, neuroprotection, and neurological functional recovery following SCI.</description><identifier>ISSN: 0893-7648</identifier><identifier>EISSN: 1559-1182</identifier><identifier>DOI: 10.1007/s12035-020-02118-7</identifier><identifier>PMID: 32964315</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Angiogenesis ; Biomedical and Life Sciences ; Biomedicine ; CCL3 protein ; Cell Biology ; Chemokines ; Compression ; Docosahexaenoic acid ; Endothelial cells ; Glial fibrillary acidic protein ; Gliosis ; Hyperalgesia ; Immunohistochemistry ; Inflammation ; Injection ; Interleukin 1 ; Interleukin 6 ; Lipopolysaccharides ; Monocyte chemoattractant protein 1 ; Neurobiology ; Neurology ; Neuroprotection ; Neurosciences ; Nitric oxide ; Pain perception ; Recovery of function ; Spinal cord injuries ; Tumor necrosis factor-α</subject><ispartof>Molecular neurobiology, 2021, Vol.58 (1), p.424-438</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020</rights><rights>Springer Science+Business Media, LLC, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-3b26845519dfc2c29976f378dc6a49324d382efe51871645befda374407224823</citedby><cites>FETCH-LOGICAL-c375t-3b26845519dfc2c29976f378dc6a49324d382efe51871645befda374407224823</cites><orcidid>0000-0002-6434-0245</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/s12035-020-02118-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12035-020-02118-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32964315$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kim, Juri</creatorcontrib><creatorcontrib>Joshi, Hari Prasad</creatorcontrib><creatorcontrib>Sheen, Seung Hun</creatorcontrib><creatorcontrib>Kim, Kyoung-Tae</creatorcontrib><creatorcontrib>Kyung, Jae Won</creatorcontrib><creatorcontrib>Choi, Hyemin</creatorcontrib><creatorcontrib>Kim, Ye Won</creatorcontrib><creatorcontrib>Kwon, Su Yeon</creatorcontrib><creatorcontrib>Roh, Eun Ji</creatorcontrib><creatorcontrib>Choi, Un Yong</creatorcontrib><creatorcontrib>Sohn, Seil</creatorcontrib><creatorcontrib>Kim, Yong Ho</creatorcontrib><creatorcontrib>Park, Chul-Kyu</creatorcontrib><creatorcontrib>Kumar, Hemant</creatorcontrib><creatorcontrib>Han, In-Bo</creatorcontrib><title>Resolvin D3 Promotes Inflammatory Resolution, Neuroprotection, and Functional Recovery After Spinal Cord Injury</title><title>Molecular neurobiology</title><addtitle>Mol Neurobiol</addtitle><addtitle>Mol Neurobiol</addtitle><description>Resolvins, a new family from the endogenous specialized pro-resolving mediators (SPMs), promote the resolution of the inflammatory response. Resolvin D3 (RvD3), a docosahexaenoic acid (DHA) product, has been known to suppress the inflammatory response. However, the anti-inflammatory and neuroprotective effects of RvD3 are not known in a model of spinal cord injury (SCI). Here, we investigated the anti-inflammatory and neuroprotective effect of RvD3 in a mouse model of SCI. Processes associated with anti-inflammation and angiogenesis were studied in RAW 264.7 cells and the human brain endothelial cell line hCMEC/D3, respectively. Additionally, female C57BL/6 mice were subjected to moderate compression SCI (20-g weight compression for 1 min) followed by intrathecal injection of vehicle or RvD3 (1 μg/20 μL) at 1 h post-SCI. RvD3 decreased the lipopolysaccharide (LPS)-induced production of inflammatory mediators and nitric oxide (NO) in RAW 264.7 cells and promoted an angiogenic effect in the hCMEC/D3 cell line. Treatment with RvD3 improved locomotor recovery and reduced thermal hyperalgesia in SCI mice compared with vehicle treatment at 14 days post-SCI. Remarkably, RvD3-treated mice exhibited reduced expression of inflammatory cytokines (TNF-α, IL6, IL1β) and chemokines (CCL2, CCL3). Also, RvD3-treated mice exhibited increased expression of tight junction proteins such as zonula occludens (ZO)-1 and occludin. Furthermore, immunohistochemistry showed a decreased level of gliosis (GFAP, Iba-1) and neuroinflammation (CD68, TGF-β) and enhanced neuroprotection. These data provide evidence that intrathecal injection of RvD3 represents a promising therapeutic strategy to promote inflammatory resolution, neuroprotection, and neurological functional recovery following SCI.</description><subject>Angiogenesis</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>CCL3 protein</subject><subject>Cell Biology</subject><subject>Chemokines</subject><subject>Compression</subject><subject>Docosahexaenoic acid</subject><subject>Endothelial cells</subject><subject>Glial fibrillary acidic protein</subject><subject>Gliosis</subject><subject>Hyperalgesia</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Injection</subject><subject>Interleukin 1</subject><subject>Interleukin 6</subject><subject>Lipopolysaccharides</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Neurobiology</subject><subject>Neurology</subject><subject>Neuroprotection</subject><subject>Neurosciences</subject><subject>Nitric oxide</subject><subject>Pain perception</subject><subject>Recovery of function</subject><subject>Spinal cord injuries</subject><subject>Tumor necrosis 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B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QR</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</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>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>M2M</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0002-6434-0245</orcidid></search><sort><creationdate>2021</creationdate><title>Resolvin D3 Promotes Inflammatory Resolution, Neuroprotection, and Functional Recovery After Spinal Cord Injury</title><author>Kim, Juri ; Joshi, Hari Prasad ; Sheen, Seung Hun ; Kim, Kyoung-Tae ; Kyung, Jae Won ; Choi, Hyemin ; Kim, Ye Won ; Kwon, Su Yeon ; Roh, Eun Ji ; Choi, Un Yong ; Sohn, Seil ; Kim, Yong Ho ; Park, Chul-Kyu ; Kumar, Hemant ; Han, In-Bo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-3b26845519dfc2c29976f378dc6a49324d382efe51871645befda374407224823</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiogenesis</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>CCL3 protein</topic><topic>Cell Biology</topic><topic>Chemokines</topic><topic>Compression</topic><topic>Docosahexaenoic acid</topic><topic>Endothelial cells</topic><topic>Glial fibrillary acidic protein</topic><topic>Gliosis</topic><topic>Hyperalgesia</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Injection</topic><topic>Interleukin 1</topic><topic>Interleukin 6</topic><topic>Lipopolysaccharides</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Neurobiology</topic><topic>Neurology</topic><topic>Neuroprotection</topic><topic>Neurosciences</topic><topic>Nitric oxide</topic><topic>Pain perception</topic><topic>Recovery of function</topic><topic>Spinal cord injuries</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kim, Juri</creatorcontrib><creatorcontrib>Joshi, Hari Prasad</creatorcontrib><creatorcontrib>Sheen, Seung Hun</creatorcontrib><creatorcontrib>Kim, Kyoung-Tae</creatorcontrib><creatorcontrib>Kyung, Jae Won</creatorcontrib><creatorcontrib>Choi, Hyemin</creatorcontrib><creatorcontrib>Kim, Ye Won</creatorcontrib><creatorcontrib>Kwon, Su Yeon</creatorcontrib><creatorcontrib>Roh, Eun Ji</creatorcontrib><creatorcontrib>Choi, Un Yong</creatorcontrib><creatorcontrib>Sohn, Seil</creatorcontrib><creatorcontrib>Kim, Yong Ho</creatorcontrib><creatorcontrib>Park, Chul-Kyu</creatorcontrib><creatorcontrib>Kumar, Hemant</creatorcontrib><creatorcontrib>Han, In-Bo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences 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>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research 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Seung Hun</au><au>Kim, Kyoung-Tae</au><au>Kyung, Jae Won</au><au>Choi, Hyemin</au><au>Kim, Ye Won</au><au>Kwon, Su Yeon</au><au>Roh, Eun Ji</au><au>Choi, Un Yong</au><au>Sohn, Seil</au><au>Kim, Yong Ho</au><au>Park, Chul-Kyu</au><au>Kumar, Hemant</au><au>Han, In-Bo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Resolvin D3 Promotes Inflammatory Resolution, Neuroprotection, and Functional Recovery After Spinal Cord Injury</atitle><jtitle>Molecular neurobiology</jtitle><stitle>Mol Neurobiol</stitle><addtitle>Mol Neurobiol</addtitle><date>2021</date><risdate>2021</risdate><volume>58</volume><issue>1</issue><spage>424</spage><epage>438</epage><pages>424-438</pages><issn>0893-7648</issn><eissn>1559-1182</eissn><abstract>Resolvins, a new family from the endogenous specialized pro-resolving mediators (SPMs), promote the resolution of the inflammatory response. Resolvin D3 (RvD3), a docosahexaenoic acid (DHA) product, has been known to suppress the inflammatory response. However, the anti-inflammatory and neuroprotective effects of RvD3 are not known in a model of spinal cord injury (SCI). Here, we investigated the anti-inflammatory and neuroprotective effect of RvD3 in a mouse model of SCI. Processes associated with anti-inflammation and angiogenesis were studied in RAW 264.7 cells and the human brain endothelial cell line hCMEC/D3, respectively. Additionally, female C57BL/6 mice were subjected to moderate compression SCI (20-g weight compression for 1 min) followed by intrathecal injection of vehicle or RvD3 (1 μg/20 μL) at 1 h post-SCI. RvD3 decreased the lipopolysaccharide (LPS)-induced production of inflammatory mediators and nitric oxide (NO) in RAW 264.7 cells and promoted an angiogenic effect in the hCMEC/D3 cell line. Treatment with RvD3 improved locomotor recovery and reduced thermal hyperalgesia in SCI mice compared with vehicle treatment at 14 days post-SCI. Remarkably, RvD3-treated mice exhibited reduced expression of inflammatory cytokines (TNF-α, IL6, IL1β) and chemokines (CCL2, CCL3). Also, RvD3-treated mice exhibited increased expression of tight junction proteins such as zonula occludens (ZO)-1 and occludin. Furthermore, immunohistochemistry showed a decreased level of gliosis (GFAP, Iba-1) and neuroinflammation (CD68, TGF-β) and enhanced neuroprotection. These data provide evidence that intrathecal injection of RvD3 represents a promising therapeutic strategy to promote inflammatory resolution, neuroprotection, and neurological functional recovery following SCI.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>32964315</pmid><doi>10.1007/s12035-020-02118-7</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-6434-0245</orcidid></addata></record> |
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| subjects | Angiogenesis Biomedical and Life Sciences Biomedicine CCL3 protein Cell Biology Chemokines Compression Docosahexaenoic acid Endothelial cells Glial fibrillary acidic protein Gliosis Hyperalgesia Immunohistochemistry Inflammation Injection Interleukin 1 Interleukin 6 Lipopolysaccharides Monocyte chemoattractant protein 1 Neurobiology Neurology Neuroprotection Neurosciences Nitric oxide Pain perception Recovery of function Spinal cord injuries Tumor necrosis factor-α |
| title | Resolvin D3 Promotes Inflammatory Resolution, Neuroprotection, and Functional Recovery After Spinal Cord Injury |
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