Ventral Epidural Stimulation Restores Forelimb Function and Reduces Microglial Activation after Subacute Cervical...

Area of Science:

• Neuroscience
• Regenerative Medicine
• Spinal Cord Injury Research

Background:

• Neuromodulation is a promising strategy for sensorimotor recovery after neural injury.
• Motor neurons crucial for movement reside in the ventral gray matter of the spinal cord.
• Targeting these neurons requires precise stimulation techniques.

Purpose of the Study:

• To investigate if ventral epidural stimulation can promote lasting recovery of skilled motor function after spinal cord injury.
• To assess the impact of ventral stimulation on motor pathways and neuronal/glial responses.
• To establish a novel approach for activating motor neurons caudal to injury.

Main Methods:

• Developed a wireless stimulation system for selective ventral epidural stimulation.
• Administered stimulation to animals with cervical spinal cord injury.
• Assessed forelimb motor function using skilled reaching tasks.
• Analyzed neuronal and microglial gene expression (Nr4a1) and morphology.

Main Results:

• Ventrally stimulated animals showed significant improvements in forelimb function.
• Stimulation activated relevant motor pathways, leading to enhanced volitional movement.
• Observed increased neuronal Nr4a1 expression and reduced microglial Nr4a1 expression.
• Detected a shift in microglial morphology towards a ramified state in the stimulated region.

Conclusions:

• Ventral spinal stimulation is effective in improving skilled motor function after spinal cord injury in an animal model.
• This approach facilitates sustained motor recovery, even when behavioral testing is separated from stimulation.
• The study provides the first evidence of successful ventral spinal stimulation for functional improvement and highlights its impact on neural and glial environments.