resolvin-d1 and Brain-Edema

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.

Topics: Animals; Anti-Inflammatory Agents; Blood-Brain Barrier; Brain; Brain Edema; Disease Models, Animal; Docosahexaenoic Acids; Immunity, Innate; Oligopeptides; Rats; Receptors, Formyl Peptide; Signal Transduction; Subarachnoid Hemorrhage