Resolvin D3 Promotes Inflammatory Resolution, Neuroprotection, and Functional Recovery After Spinal Cord Injury
- Authors
- Kim, J.; Joshi, H.P.; Sheen, S.H.; Kim, K.-T.; Kyung, J.W.; Choi, H.; Kim, Y.W.; Kwon, S.Y.; Roh, E.J.; Choi, U.Y.; Sohn, S.; Kim, Y.H.; Park, C.-K.; Kumar, H.; Han, I.-B.
- Issue Date
- Jan-2021
- Publisher
- Springer
- Keywords
- Inflammatory response; Pain; Resolvin D3; Resolvins; Secondary injury; Spinal cord injury
- Citation
- Molecular Neurobiology, v.58, no.1, pp.424 - 438
- Journal Title
- Molecular Neurobiology
- Volume
- 58
- Number
- 1
- Start Page
- 424
- End Page
- 438
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/79394
- DOI
- 10.1007/s12035-020-02118-7
- ISSN
- 0893-7648
- 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. © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
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