title: Deep brain stimulation of the midbrain locomotor region improves paretic hindlimb function after spinal cord injury in rats.
abstract: In severe spinal cord injuries, the tracts conveying motor commands to the spinal cord are disrupted, resulting in paralysis, but many patients still have small numbers of spared fibers. We have found that excitatory deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), an important control center for locomotion in the brain, markedly improved hindlimb function in rats with chronic, severe, but incomplete spinal cord injury. The medial medullary reticular formation was essential for this effect. Functional deficits of rats with 20 to 30% spared reticulospinal fibers were comparable to patients able to walk but with strong deficits in strength and speed [for example, individuals with American Spinal Injury Association Impairment Scale (AIS)-D scores]. MLR DBS enabled close to normal locomotion in these rats. In more extensively injured animals, with less than 10% spared reticulospinal fibers, hindlimbs were almost fully paralyzed, comparable to wheelchair-bound patients (for example, AIS-A, B, and C). With MLR DBS, hindlimb function reappeared under gravity-released conditions during swimming. We propose that therapeutic MLR DBS using the brain's own motor command circuits may offer a potential new approach to treat persistent gait disturbances in patients suffering from chronic incomplete spinal cord injury.
authors.affiliation: Brain Research Institute, University of Zurich, 8057 Zurich, Switzerland.
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Bachmann
authors.forename: Alina
authors.initials: A
authors.lastname: Matis
authors.forename: Nicolas T
authors.initials: NT
authors.lastname: Lindau
authors.forename: Petra
authors.initials: P
authors.lastname: Felder
authors.forename: Miriam
authors.initials: M
authors.lastname: Gullo
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000473:pathology / Q000503:physiopathology; D046690:Deep Brain Stimulation; D006614:Hindlimb / Q000502:physiology* / Q000503:physiopathology*; D008124:Locomotion / Q000502:physiology*; D008159:Lumbar Vertebrae / Q000473:pathology / Q000503:physiopathology; D008636:Mesencephalon / Q000473:pathology / Q000503:physiopathology*; D010291:Paresis / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D013550:Swimming; D013997:Time Factors; D016138:Walking