Deep Brain Stimulation of the Mesencephalic Locomotor Region
Funded in: 2017, 2018, 2019
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Problem: Currently no treatment for incomplete spinal cord injury exists, evidenced by the large number of wheelchair-bound patients worldwide.
Target: Brainstem nuclei controlling locomotion and projecting to the spinal cord below the level of injury
Goal: Improvement of motor function in incomplete SCI
Functionally or anatomically incomplete spinal cord injury (SCI), characterized by sparing of some fibers still connecting the brain with the spinal cord caudal to the lesion, affects millions of people worldwide. Loss or severe impairment of motor control and locomotion is common, with limited potential for functional recovery.
As a novel, previously unattended strategy for the treatment of large but incomplete spinal cord injuries our lab suggests the combination of two strategies:
1) use of deep brain stimulation (DBS)
2) with focus on a small region in the midbrain known to initiate and control locomotion (mesencephalic locomotor region, MLR)
Electrical deep brain stimulation is a procedure in which electrodes are stereotaxically implanted into deep brain areas. DBS of basal ganglia targets is nowadays a routine treatment for drug resistant Parkinson’s disease. It is successfully applied in thousands of patients showing remarkable results, and is currently becoming a treatment strategy also for certain neuropsychiatric disorders.
Acute electrical stimulation experiments in rats with large but incomplete, chronic spinal cord injury recently conducted in our lab showed that deep brain stimulation of the MLR in the brainstem acutely improves hindlimb locomotor function, even in case of subtotal spinal cord injury. On the other hand, electrical activity has been shown to increase injury-induced plasticity in the mature central nervous system. Thus we hypothesize that electrically stimulating spared axons after incomplete SCI via the MLR can enhance anatomical rearrangement and thus lead to permanent functional improvements.
The main goal of this project is to evaluate the potential of stimulation of the MLR locomotor control center as a novel treatment for deficient locomotion in spinal cord injured rats. The project will provide important foundations for a currently planned clinical trial in severe ASIA B and C SCI patients.