期刊
MOLECULAR NEUROBIOLOGY
卷 58, 期 5, 页码 1963-1977出版社
SPRINGER
DOI: 10.1007/s12035-020-02237-1
关键词
Resolvin D1; Subarachnoid hemorrhage; Inflammation; Early brain injury; Formyl peptide receptor 2 (FPR2)
资金
- National Natural Science Foundation of China (NSFC) [81870922, 81771291]
- Medical Science and Technology Development Foundation, Nanjing Department of Health [JQX18001]
- Fundamental Research Funds for the Central Universities [021414380361]
The study found that Resolvin D1 (RvD1) has a strong anti-inflammatory effect on early brain injury (EBI) following subarachnoid hemorrhage (SAH), significantly reducing neutrophil infiltration and pro-inflammatory activation of microglia. This leads to notable improvements in neurological function and brain tissue restoration.
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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