Effects on Locomotion, Muscle, Bone, and Blood Induced by a Combination Therapy Eliciting Weight-Bearing Stepping in Nonassisted Spinal Cord–Transected Mice

Background. The health benefits associated with physical activity–based rehabilitation in patients with no lower-extremity motor function after a spinal cord injury (SCI) is uncertain. Methods. The authors assessed signs of efficacy, safety, and utility associated with a novel pharmacological combin...

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Bibliographic Details
Published in:Neurorehabilitation and neural repair 2011-03, Vol.25 (3), p.234-242
Main Authors: Guertin, Pierre A., Ung, Roth-Visal, Rouleau, Pascal, Steuer, Inge
Format: Article
Language:English
Subjects:
Animals
Combined Modality Therapy - adverse effects
Disease Models, Animal
Exercise Therapy - methods
Lameness, Animal - drug therapy
Lameness, Animal - therapy
Male
Mice
Paralysis - drug therapy
Paralysis - rehabilitation
Physical Therapy Modalities
Spinal Cord Injuries - drug therapy
Spinal Cord Injuries - rehabilitation
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Summary:Background. The health benefits associated with physical activity–based rehabilitation in patients with no lower-extremity motor function after a spinal cord injury (SCI) is uncertain. Methods. The authors assessed signs of efficacy, safety, and utility associated with a novel pharmacological combination therapy to activate central pattern generator (CPG) activity and corresponding locomotor activity in complete thoracic Th9/10-transected mice. Results. Subcutaneous administration 4 times per week for 1 month of 1.5 mg/kg buspirone, 1.5 mg/kg apomorphine, 12.5 mg/kg benserazide, and 50 mg/kg L-DOPA induced episodes of weight-bearing stepping on a treadmill in nonassisted paraplegic mice for 45-minute sessions. Hindlimb muscle cross-sectional area and fiber area values as well as several blood cell constituent levels assessed at 30 days postinjury were positively affected by the combination therapy, as compared with controls. Episodes of locomotion remained effective on each treatment. Femoral bone mineral density loss was not prevented by triple therapy. Conclusion. Although translation of these findings needs further experimentation, similar pharmacological activation of the CPG offers a novel therapeutic target to provide some health benefits in motor-complete SCI patients.
ISSN:1545-9683
1552-6844
DOI:10.1177/1545968310378753