Inflammation resolution and specialized pro-resolving lipid mediators in CNS diseases

ABSTRACT

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 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 to investigate basic, critical issues such as safety.

KEYWORDS:

• Central nervous system disorders
• inflammation
• resolution of inflammation
• specialized pro-resolving lipid mediators

Article Highlights

• Acute or chronic inflammation exists in numerous CNS diseases; this can lead to neuronal loss and functional deformities through neutrophil infiltration, enhanced apoptosis, and pro-inflammatory mediator release.

• SPMs are reported to be downregulated in post-mortem studies and this provides new insights into underlying pathogenesis.

• Inflammation resolution emerges naturally after the acute phase of inflammation; it sustains long-lasting resolution by decreasing pro-inflammatory mediators and by promoting the healing process.

• SPMs accelerate inflammation resolution in CNS diseases and their application effectively ameliorates inflammatory impairments in acute and chronic animal models of neurological diseases.

• SPMs mainly function via the promotion of pathways associated with anti-inflammation, anti-oxidative stress, cell survival, DNA repair, efferocytosis, autophagy, anti-apoptosis, and tissue regeneration.

• Nanotechnology and adjuvant therapies offer opportunities for the clinical translation of SPMs.

This box summarizes key points contained in the article.

Acknowledgments

We would like to thank Editage [www.editage.cn] for English language editing.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The work of the authors was supported by the National Key R&D Program of China, grant No. [2017YFC0110304]; National Science Foundation of China, Grant No. [31600820 and No. 81701158]; The Health and Family Planning Commission of Jilin Province, Grant No. [2016Q036]; and The Science and technology planning project of Jilin Province, Grant No. [20180520110JH].