Alzheimer’s disease (AD) is one of the most common neurodegenerative disease. Accumulating evidences suggest an active role of inflammation in the pathogenesis of AD. Inflammation resolution is an active process that terminates inflammation and facilitates the restoration of inflamed tissue to homeostasis. Resolution of inflammation has been shown to be conducted by a group of specialized pro-resolving lipid mediators (SPMs) including lipoxins, resolvins, protectins, and maresins (MaRs). Recent studies have demonstrated that failure of inflammation resolution can lead to chronic inflammation and, hence, contribute to AD progression. We have previously shown that MaR1 can improve neuronal survival and increase microglial phagocytosis of Aβ. However, the effects of MaR1 on animal models of AD have not been reported. In this study, we aim to investigate the effects of MaR1 on behavioral deficits and pathological changes in a mouse model of AD. Mice received bilateral injections of Aβ₄₂ protein into the hippocampus, followed by administration of MaR1 by intra-cerebroventricular injection. The behavioral changes in the mice were analyzed using Morris water maze. Immunohistochemistry, Fluoro-Jade B (FJB) staining, cytometric beads array (CBA), and western blot analysis were used to demonstrate molecular changes in the mice hippocampus and cortex. Our results showed that MaR1 treatment significantly improved the cognitive decline, attenuated microglia and astrocyte activation. In addition, we found that MaR1 decreased the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1 production induced by Aβ42 and increased the anti-inflammatory cytokines IL-2, IL-10 secretion with or without Aβ42 stimulation. Moreover, western blot results showed that MaR1 up-regulated the levels of proteins related to survival pathway including PI3K/AKT, ERK and down-regulated the levels of proteins associated with inflammation, autophagy, and apoptosis pathways such as p38, mTOR and caspase 3. To conclude, MaR1 improved the cognitive decline, ameliorated pro-inflammatory glia cells activation via improving survival, enhancing autophagy, inhibiting inflammation and apoptosis pathways. In conclusion, this study shows that inflammation resolution may be a potential therapeutic target for AD.

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss and dementia. Accumulating evidence suggests that inflammation is involved in the pathogenesis of AD. Epidemiological studies suggest that use of anti-inflammatory drugs is associated with a lower incidence of AD. However, clinical trials with anti-inflammatory drugs have not been successful. Recent studies have shown that inflammation is resolved by a process that is mediated by a group of lipid mediators, so called specialized pro-resolving lipid mediators (SPMs). Unlike anti-inflammatory strategies, which usually involve inhibition of the synthesis of inflammatory mediators, stimulating the resolution of inflammation is aimed at ending inflammation in a similar fashion as under normal physiological conditions. We have previously shown that pathways of resolution are impaired in AD. Moreover, we found that SPMs can improve neuronal survival and increase microglial phagocytosis of amyloid beta (Aβ) in in vitro studies, indicating that stimulating resolution of inflammation may be a potential therapeutic target in AD. In this review, we summarize recent findings regarding resolution of inflammation in AD. We also discuss possible strategies to stimulate the resolution of inflammation in AD, specifically focusing on signaling pathways, including SPMs, their receptors and enzymes involved in their formation.

: The role of gut microbiota in health and diseases has been receiving increased attention recently. Emerging evidence from previous studies on gut-microbiota-brain axis highlighted the importance of gut microbiota in neurological disorders. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS) resulting from T-cell-driven, myelin-directed autoimmunity. The dysbiosis of gut microbiota in MS patients has been reported in published research studies, indicating that gut microbiota plays an important role in the pathogenesis of MS. Gut microbiota have also been reported to influence the initiation of disease and severity of experimental autoimmune encephalomyelitis, which is the animal model of MS. However, the underlying mechanisms of gut microbiota involvement in the pathogenesis of MS remain unclear. Therefore, in this review, we summerized the potential mechanisms for gut microbiota involvement in the pathogenesis of MS, including increasing the permeability of the intestinal barrier, initiating an autoimmune response, disrupting the blood-brain barrier integrity, and contributing to chronic inflammation. The possibility for gut microbiota as a target for MS therapy has also been discussed. This review provides new insight into understanding the role of gut microbiota in neurological and inflammatory diseases.

Ischemic stroke contributes to ~80% of all stroke cases. Recanalization with thrombolysis or endovascular thrombectomy are currently critical therapeutic strategies for rebuilding the blood supply following ischemic stroke. However, recanalization is often accompanied by cerebral ischemia reperfusion injury that is mediated by oxidative stress and inflammation. Resolution of inflammation belongs to the end stage of inflammation where inflammation is terminated and the repair of damaged tissue is started. Resolution of inflammation is mediated by a group of newly discovered lipid mediators called specialized pro-resolving lipid mediators (SPMs). Accumulating evidence suggests that SPMs decrease leukocyte infiltration, enhance efferocytosis, reduce local neuronal injury, and decrease both oxidative stress and the production of inflammatory cytokines in various in vitro and in vivo models of ischemic stroke. In this review, we summarize the mechanisms of reperfusion injury and the various roles of SPMs in stroke therapy.

Introduction: Inflammation resolution induced by specialized pro-resolving lipid mediators (SPMs) is a new concept. The application of SPMs is a promising therapeutic strategy that can potentially supersede anti-inflammatory drugs. Most CNS diseases are associated with hyperreactive inflammatory damage. CNS inflammation causes irreversible neuronal loss and permanent functional impairments. Given the high mortality and morbidity rates, the investigation of therapeutic strategies to ameliorate inflammatory damage is necessary. Areas covered: In this review, we explore inflammation resolution in CNS disorders. We discuss the underlying mechanisms and dynamic changes of SPMs and their precursors in neurological diseases and examine how this can potentially be incorporated into the clinic. References were selected from PubMed; most were published between 2010 and 2019. Expert opinion: Inflammation resolution is a natural process that emerges after acute or chronic inflammation. The is evidence that SPMs can effectively ameliorate hyperreactive inflammation, shorten resolution time and accelerate tissue regeneration in CNS disorders. Adjuvants and nanotechnology offer opportunities for SPM drug design; however, more preclinical studies are necessary investigate basic, critical issues such as safety.