Maresin 1 Promotes Inflammatory Resolution, Neuroprotection, and Functional Neurological Recovery After Spinal Cord Injury

The Journal of Neuroscience, 2017 · DOI: 10.1523/JNEUROSCI.1395-17.2017 · Published: November 29, 2017

Simple Explanation

Spinal cord injury (SCI) often leads to incomplete resolution of inflammation, which further damages tissue and hinders recovery. This study investigates whether Maresin 1 (MaR1), a specialized proresolving mediator (SPM), can promote inflammation resolution and improve neurological outcomes after SCI. The research demonstrates that after SCI in mice, the body's own production of SPMs is not adequately triggered at the injury site. Administering MaR1 helps to clear inflammatory cells, reduces the levels of pro-inflammatory molecules, and shifts the behavior of immune cells towards tissue repair. Ultimately, MaR1 treatment led to significant improvements in locomotor recovery and reduced secondary tissue damage. The findings suggest that therapies aimed at promoting inflammation resolution could be a promising new approach for treating acute SCI.

Study Duration

28 days

Participants

142 adult (8–10 weeks old) female C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
SPM biosynthesis is impaired after SCI, with delayed synthesis of SPMs derived from AA, DHA, and EPA.
2
Systemic administration of MaR1 enhances the elimination of peripheral myeloid cells (neutrophils and macrophages) from the injured spinal cord.
3
MaR1 reduces tissue damage, increases myelin content, enhances axonal sparing, reduces demyelination, and improves neuronal survival after SCI.

Research Summary

The study investigates the effect of Maresin 1 (MaR1) on inflammatory resolution and neurological recovery after spinal cord injury (SCI) in mice. It was found that the biosynthesis of specialized proresolving mediators (SPMs) is impaired after SCI. Systemic administration of MaR1 enhanced the resolution of inflammation by accelerating neutrophil clearance and reducing macrophage accumulation. It also modulated cytokine expression and intracellular signaling pathways. MaR1 treatment led to improved locomotor recovery and reduced secondary tissue damage, suggesting that immunoresolvent therapies could be a novel approach for improving neurological recovery after acute SCI.

Practical Implications

Therapeutic Potential

MaR1 and other SPMs could be developed as novel therapeutic agents to treat acute SCI and other neurological conditions where inflammation plays a significant role.

Immunoresolvent Therapies

The study supports the development of immunoresolvent therapies to address the dysregulated inflammatory response after SCI.

Clinical Translation

The findings suggest that promoting inflammation resolution could improve functional outcomes in SCI patients, for whom effective treatments are currently lacking.

Study Limitations

1
The study was conducted on female mice, and results may not be directly applicable to males.
2
The long-term effects of MaR1 administration after SCI were not investigated.
3
The precise mechanisms by which MaR1 exerts its pro-resolving and neuroprotective effects require further elucidation.

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