Gabapentinoid treatment promotes corticospinal plasticity and regeneration following murine spinal cord injury

The Journal of Clinical Investigation, 2020 · DOI: https://doi.org/10.1172/JCI130391 · Published: January 1, 2020

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injuries disrupt communication between the brain and spinal cord, leading to neurological deficits and long-term disability. Currently, there are no treatments to restore function after SCI. This study found that the α2δ2 subunit of voltage-gated calcium channels inhibits axon growth and regeneration in corticospinal neurons. Blocking α2δ2 with gabapentin promoted corticospinal structural plasticity and regeneration in adulthood. Mice treated with gabapentin recovered upper extremity function after cervical SCI. This recovery depends on the reorganization of the corticospinal pathway.

Study Duration

4 months

Participants

Adult female and male C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
The α2δ2 subunit negatively regulates axon growth and regeneration of corticospinal neurons.
2
Gabapentin administration promoted sprouting and regeneration of corticospinal axons in adulthood.
3
Mice administered gabapentin recovered upper extremity function after cervical SCI.

Research Summary

Axon regeneration failure causes neurological deficits and long-term disability after spinal cord injury (SCI). Here, we found that the α2δ2 subunit of voltage-gated calcium channels negatively regulates axon growth and regeneration of corticospinal neurons, the cells that originate the corticospinal tract. Mice administered gabapentin recovered upper extremity function after cervical SCI.

Practical Implications

Potential Therapeutic Target

Targeting α2δ2 with gabapentinoids may aid in the repair of motor circuits after SCI.

Repurposing Existing Drugs

Gabapentinoids, already used clinically, show promise as a novel treatment for SCI repair.

Early Intervention Importance

Early administration of gabapentinoids may maximize functional recovery after CNS trauma.

Study Limitations

1
Study was conducted in mice, and results may not directly translate to humans.
2
The design of the electrode arrays enabled us to record neuronal firing within cortical layer V, but neurons other than corticospinal neurons may also be recorded.
3
Further dissection of the mechanisms underlying changes in α2δ2 expression will be an important direction for future investigations.

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