Resident immune responses to spinal cord injury: role of astrocytes and microglia

NEURAL REGENERATION RESEARCH, 2024 · DOI: https://doi.org/10.4103/1673-5374.389630 · Published: December 11, 2023

Simple Explanation

Spinal cord injury (SCI) can be caused by a myriad of events and results in a debilitating loss of neurologic function. This review synthesizes recent data on the critical roles played by astrocytes and microglia in wound corralling, lesion containment and regeneration Resident immune cells are first responders to acute injury and chief regulators of immune responses in the chronic phase.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Following SCI, increased extracellular ATP serves as a damage-associated molecular pattern signal molecule as it is released from ruptured and apoptotic cells.
2
Astrocytes play major roles in injury as they are chief regulators of inflammation through their maintenance of the BBB and the containment of lesion sites
3
In both injurious and homeostatic conditions, astrocytes are intricately connected with neuronal function in the context of the tripartite synapse, where they modulate neurotransmission between pre- and postsynaptic neurons

Research Summary

Spinal cord injury can be traumatic or non-traumatic in origin, with the latter rising in incidence and prevalence with the aging demographics of our society. Understanding key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential. By summarizing key areas of debate including M1/M2 and A1/A2 polarization, and gliotransmission, we highlight current knowledge and outstanding questions in glial biology.

Practical Implications

Therapeutic Target Development

Glia, specifically astrocytes and microglia, are critical therapeutic targets due to their extensive structural and functional roles in the nervous system after SCI.

Combinatorial Pharmacotherapy

Combinatorial pharmacotherapy may be used to modulate endogenous immune responses after SCI.

Personalized Medicine

Untangling region-specific responses of glial cells across time to optimize functional outcomes and enhance treatment capabilities for SCI patients.

Study Limitations

1
Host glial cell responses to grafted cells are not well characterized.
2
The mechanisms of permeability regulation [of the blood brain barrier] are incompletely understood.
3
Due to the complex and rapidly changing inflammatory milieu that follows nerve injury and SCI, it is difficult to evaluate the effects of individual signaling pathways independent of the various cell-mediated responses occurring around them.

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