Mitochondrial function in spinal cord injury and regeneration

Cellular and Molecular Life Sciences, 2022 · DOI: https://doi.org/10.1007/s00018-022-04261-x · Published: April 13, 2022

Regenerative Medicine Neurology Genetics

Simple Explanation

Spinal cord injury (SCI) leads to paralysis and affects life quality and expectancy. The central nervous system (CNS), including the spinal cord, cannot regenerate in mammals, hindering full recovery. The injury progresses in two phases: an initial mechanical insult and a secondary phase of escalating damage. Mitochondria play a central role in cellular responses following SCI. Mitochondrial dysfunction contributes to cell death, cellular metabolism impacts the immune response, mitochondrial presence relates to axon regeneration, and mitochondrial function regulates neural stem cell activity. This review explores the cellular responses during SCI's secondary phase and the involvement of mitochondria in these responses. It also examines the role of mitochondria in spinal cord regeneration, suggesting further research into mitochondrial function for potential SCI treatments.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Mitochondrial dysfunction is a common event in different triggers leading to cell death after SCI.
2
Cellular metabolism regulates the immune response after SCI.
3
Mitochondrial number and localization correlate with axon regenerative capacity.

Research Summary

Spinal cord injury induces mitochondrial dysfunction, resulting in ROS generation, loss of bioenergetics, and cell death, that together with the initial damage, induce a switch towards a glycolytic metabolism, activating the neurotoxic M1 immune response and inflammation, which further induces cell death due to the release of pro-inflammatory cytokines and reactive species. In non-regenerative models, excessive cell death is observed, M2 immune response at attempted, but only to attain a predominant M1 immune response and chronic inflammation. Mitochondria are not able to elicit an adaptive response, showing mitochondrial dysfunction, reduced mitochondrial trafficking, and therefore, loss of bioenergetics, resulting in further cell death and inability to regenerate the spinal cord. In regenerative models, the cell death and reactive species are necessary for precursor cell proliferation, while phagocytosis of dying cells induces a new metabolic switch towards OXPHOS and FAO utilization, and mitochondrial biogenesis, allowing the polarization to a neuroprotective M2 response, which is needed for resolving inflammation and for induction of tissue remodeling and repair.

Practical Implications

Therapeutic Target Identification

In-depth study of mitochondrial function and regulation is needed to identify potential targets for SCI therapeutic intervention.

Mitochondrial Modulation

Modulation of mitochondrial function could have a pivotal role in the design of novel therapeutical approaches to enhance spinal cord regeneration.

Personalized Treatment Strategies

Understanding the mitochondrial response after axotomy is highly important for personalized treatment strategies.

Study Limitations

1
Most studies are made in rodents, limiting direct translation to humans.
2
Estimation of spinal cord injury prevalence is not completely reliable.
3
Lack of full understanding of factors that accompany SCI limits therapeutic development.

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