The beneﬁts of neuroinﬂammation for the repair of the injured central nervous system

Cellular & Molecular Immunology, 2019 · DOI: https://doi.org/10.1038/s41423-019-0223-3 · Published: March 15, 2019

Regenerative Medicine Immunology Neurology

Simple Explanation

Neuroinflammation, once viewed solely as detrimental, is now recognized to have beneficial aspects for CNS recovery after injury. This includes preservation of CNS constituents, proliferation of neural precursor populations, axonal regeneration, and myelin reformation. Following injury to the central nervous system (CNS), leukocytes infiltrate the injury site and microglia activate, triggering neuroinflammation. While excessive inflammation can be destructive, inflammatory responses in other tissues are often natural healing processes. This review highlights neuroinflammation's beneficial role in CNS recovery, focusing on neurogenesis, axonal regeneration, and remyelination. It also explores the mechanisms making neuroinflammation pro-regenerative and discusses treatment strategies.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Neuroinflammation promotes neurogenesis by influencing the formation of new neurons, with T lymphocytes playing a role in learning-induced hippocampal neurogenesis.
2
Neuroinflammation facilitates axonal regeneration by enabling immune cell subsets to alter the CNS microenvironment, promoting axonal elongation and plasticity after spinal cord injury.
3
Neuroinflammation is critical for remyelination, as immune cells support oligodendrocyte repopulation. Both M1 and M2 macrophage/microglia phenotypes have roles in remyelination.

Research Summary

Neuroinflammation, a hallmark of neurological disorders, can be both detrimental and beneficial to the central nervous system (CNS). While excessive inflammation can cause injury and death to neural elements, aspects of the neuroinflammatory response can also foster CNS recovery after neural injury. Neuroinflammation promotes neurogenesis, axonal regeneration, and remyelination through various mechanisms, including the production of trophic factors, phagocytic clearance of debris, and removal of inhibitory molecules. Harnessing the benefits of neuroinflammation requires strategies to polarize immune subsets, enhance phagocytic removal of debris, and target specific properties of activated immune cells at different stages of neurological conditions.

Practical Implications

Therapeutic Strategies

Existing medications like glatiramer acetate (GA) and interferon-β can polarize immune subsets into regulatory/anti-inflammatory phenotypes, promoting neuroprotection and regeneration.

Phagocytic Removal

Therapies enhancing phagocytic removal of cellular debris and inhibitory molecules like CSPGs (e.g., bexarotene, chondroitinase-ABC) hold promise for CNS regeneration.

Targeted Treatment

Targeting specific properties of activated immune cells and considering the timing of treatment are crucial for maximizing the benefits of neuroinflammation in CNS recovery.

Study Limitations

1
The complexity of neuroinflammation requires careful consideration of the timing and properties of immune cell activation.
2
Translating findings from animal models to human conditions poses a significant challenge.
3
Further research is needed to fully elucidate the mechanisms underlying the benefits of neuroinflammation for CNS regeneration.

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