Glial-Neuronal Interactions in Pathogenesis and Treatment of Spinal Cord Injury

International Journal of Molecular Sciences, 2021 · DOI: 10.3390/ijms222413577 · Published: December 17, 2021

Simple Explanation

Spinal cord injury (SCI) triggers an inflammatory response involving various cell types. This response is initiated by macrophages and microglia, leading to dysregulation within the injury site and adjacent spinal cord tissue. This review examines how different signaling molecules released by microglia, astrocytes, and blood inflammatory cells contribute to the death of neurons in the surrounding tissue after SCI. Astrocytes and microglia interact after SCI, with each cell type having the ability to activate the other and control their functions. The review also highlights how reactive microglia and astrocytes transform into neuroprotective phenotypes, which are important for spontaneous recovery of movement after SCI. The review suggests ways to modulate inflammation and discusses therapeutic approaches to improve outcomes after SCI. The response to spinal cord trauma involves molecular pathways activated soon after SCI, spreading throughout the spinal cord. After SCI, neutrophils infiltrate the injury site, producing neurotoxic effects. Neurons and glia synthesize pro-inflammatory cytokines, leading to inflammation and the death of neurons and oligodendrocytes.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Proliferating microglia are a key cellular component of the microglial scar which develops during the first week post-SCI to protect neural tissue.
2
Modulation of reactive microglia/astrocytes into their neuroprotective phenotypes contributes to spontaneous locomotor recovery after SCI.
3
Early modulation of the inflammatory response after SCI could be an important step towards more successful treatment of traumatic SCI.

Research Summary

This review focuses on microglia-astrocyte crosstalk and glial-neuronal interactions in an acute inﬂammatory response after spinal cord injury (SCI). The review highlights the time-dependent transformation of reactive microglia and astrocytes into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. The review also discusses promising strategies for spinal cord repair, including modulation of inﬂammatory response, addressing gut dysbiosis, electrostimulation, and rehabilitation.

Practical Implications

Therapeutic Targeting of Microglia/Astrocyte Polarization

The review suggests that therapeutic strategies could focus on promoting the polarization of microglia and astrocytes towards neuroprotective phenotypes (M2 and A2) to enhance recovery after SCI.

Early Intervention Strategies

The importance of early modulation of the inflammatory response is highlighted, suggesting that immediate post-injury treatments aimed at reducing inflammation could improve outcomes.

Gut Microbiome Modulation

The review proposes that modulating the gut microbiome could be a potential therapeutic avenue to reduce inflammation and improve recovery after SCI, given the link between SCI-induced gut dysbiosis and inflammation.

Study Limitations

1
The review relies on existing literature, which may have inherent biases or limitations.
2
The review primarily focuses on animal models of SCI, and the findings may not directly translate to human SCI.
3
The precise molecular mechanisms involved in glial-neuronal interactions and the transformation of glial phenotypes are still not fully understood.

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