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 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.


CONCLUSIONS
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.
Guertin
Pierre A
PA
Laval University Medical Center, Québec City, QC, Canada. Pierre.Guertin@crchul.ulaval.ca
Ung
Roth-Visal
RV
Rouleau
Pascal
P
Steuer
Inge
I
D000818:Animals; D003131:Combined Modality Therapy / Q000009:adverse effects; D004195:Disease Models, Animal; D005081:Exercise Therapy / Q000379:methods*; D007794:Lameness, Animal / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D051379:Mice; D010243:Paralysis / Q000188:drug therapy / Q000534:rehabilitation; D026741:Physical Therapy Modalities; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000534:rehabilitation*