Hypothalamic deep brain stimulation augments walking after spinal cord injury

Area of Science:

• Neuroscience
• Regenerative Medicine
• Neurological Rehabilitation

Background:

• Spinal cord injury (SCI) impairs walking by disrupting brain-spinal cord communication.
• Identifying brain targets is crucial for enhancing motor function recovery after SCI.

Purpose of the Study:

• To identify brain regions that regulate walking recovery post-incomplete SCI.
• To explore the therapeutic potential of targeting these regions for functional restoration.

Main Methods:

• Constructed a brain-wide atlas of active, spinal cord-projecting neurons during walking recovery.
• Investigated the role of lateral hypothalamus (LH) glutamatergic neurons (LH^Vglut2).
• Developed and tested deep brain stimulation of the LH (DBS^LH) in rodent models and a pilot human study.

Main Results:

• The LH atlas identified LH^Vglut2 neurons as key to walking recovery.
• Augmenting LH^Vglut2 neuron activity improved walking in SCI models.
• DBS^LH demonstrated immediate and durable walking improvements in animals and humans, alongside rehabilitation.
• Pilot human study showed no serious adverse events.

Conclusions:

• Targeting specific brain regions, like the LH, can enhance spinal cord-projecting neuron engagement for neurological recovery.
• DBS^LH shows promise as a novel therapy for SCI-induced walking deficits.
• Further clinical trials are needed to confirm safety and efficacy.