Abstract
Excessive inflammation is a major cause contributing to early brain injury (EBI) and is associated with negative or catastrophic outcomes of subarachnoid hemorrhage (SAH). Resolvin D1 (RvD1) exerts strong anti-inflammatory and pro-resolving effects on either acute or chronic inflammation of various origin. Henceforth, we hypothesized that RvD1 potentially attenuates excessive inflammation in EBI following SAH. Therefore, we generated a filament perforation SAH model and administered 3 different doses (0.3, 0.6, and 1.2 nmol) of RvD1 after experimental SAH. Neurological scores, brain edema, and blood–brain barrier integrity were evaluated; besides, neutrophil infiltration, neuronal deaths, and microglial pro-inflammatory polarization were observed using histopathology or immunofluorescence staining, western blots, and qPCR. After confirming the effectiveness of RvD1 in SAH, we administered the FPR2-specific antagonist Trp-Arg-Trp-Trp-Trp-Trp-NH2 (WRW4) 30 min before SAH establishment to observe whether this compound could abolish the anti-inflammatory effect of RvD1. Altogether, our results showed that RvD1 exerted a strong anti-inflammatory effect and markedly reduced neutrophil infiltration and microglial pro-inflammatory activation, leading to remarkable improvements in neurological function and brain tissue restoration. After addition of WRW4, the anti-inflammatory effects of RvD1 were abolished. These results indicated that RvD1 could exert a good anti-inflammatory effect and alleviate EBI, which suggested that RvD1 might be a novel therapeutic alternative for SAH-induced injury.
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The datasets supporting the conclusions of this article are included within the article (and its additional file).
Abbreviations
- RvD1:
-
Resolvin D1
- SAH:
-
Subarachnoid hemorrhage
- EBI:
-
Early brain injury
- i.c.v. :
-
Intracerebroventricular
- FPR2:
-
Formyl peptide receptor 2
- WRW4:
-
Trp-Arg-Trp-Trp-Trp-Trp-NH2 (WRWWWW)
- IL-1β:
-
Interleukin 1 beta
- TNF-α:
-
Tumor necrosis factor alpha
- NLRP3:
-
NLR family pyrin domain containing 3
- iNOS:
-
Induced nitric oxide synthases
- MPO:
-
Myeloperoxidase
- ICAM-1:
-
Intercellular adhesion molecule 1
- CINC-1:
-
Cytokine-induced neutrophil chemoattractant 1
- CXCL-2:
-
C-X-C motif chemokine 2
- MCP-1:
-
Monocyte chemotactic protein 1
- IBA-1:
-
Ionized calcium binding adaptor molecule-1
- GFAP:
-
Glial fibrillary acidic protein
- DHA:
-
Docosahexaenoic acid
- H&E:
-
Hematoxylin-eosin staining
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- TRAF6:
-
TNF receptor associated factor 6
- RRIDs:
-
Research resource identifiers
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Funding
This work was supported by grants from the National Natural Science Foundation of China (NSFC): No. 81870922 (Wei Li); No. 81771291 (Chun-Hua Hang); Medical Science and Technology Development Foundation, Nanjing Department of Health: No. JQX18001 (Wei Li); and the Fundamental Research Funds for the Central Universities No. 021414380361 (Wei Li).
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G-J L is responsible for study design, performing experiments, manuscript drafting; TT analyses and interprets of results; X-S Z is responsible for animal management and drug administration; YL and L-Y W are responsible for statistical analysis; Y-Y G and HW are responsible for cell culture; H-B D is responsible for immunofluorescence staining; YZ is responsible for neurological evaluation; ZZ is responsible for primary reversion of manuscript; C-H H is responsible for study design; WL is responsible for study design and critical revision of manuscript; all authors read and approved the final manuscript.
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Liu, GJ., Tao, T., Zhang, XS. et al. Resolvin D1 Attenuates Innate Immune Reactions in Experimental Subarachnoid Hemorrhage Rat Model. Mol Neurobiol 58, 1963–1977 (2021). https://doi.org/10.1007/s12035-020-02237-1
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DOI: https://doi.org/10.1007/s12035-020-02237-1