Combined effects of neurotrophin secreting transplants, exercise, and serotonergic drug challenge improve function in spinal rats.
OBJECTIVE
To determine the effects of neurotrophin-secreting transplants combined with exercise and serotonergic drug challenges on recovery of hindlimb function in rats with midthoracic spinal cord transection injuries.


METHODS
Spinalized animals received transplants of fibroblasts genetically modified to express brain-derived neurotrophic factor and neurotrophin-3 and daily cycling exercise. Hindlimb movement in an open-field test (BBB) was scored weekly. Serotonin agonists were used monthly to further stimulate motor function. Axonal growth was quantified in the transplant and at L5 using immunocytochemical markers. Weights of hindlimb muscles were used to assess muscle atrophy.


RESULTS
Neurotrophin-secreting transplants stimulated axonal growth, and cycling prevented muscle atrophy, but individual treatments did not improve motor scores. Combined treatments resulted in improvements in motor function. Serotonergic agonists further improved function in all groups, and transplant groups with exercise achieved weight-supporting levels following drug treatment.


CONCLUSIONS
Combined treatments, but not individual treatments, improved hindlimb function.
Nothias
J-M
JM
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Mitsui
T
T
Shumsky
J S
JS
Fischer
I
I
Antonacci
M D
MD
Murray
M
M
D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation*; D009414:Nerve Growth Factors / Q000502:physiology*; D010805:Physical Conditioning, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000628:therapy*; D013904:Thoracic Vertebrae
D009414:Nerve Growth Factors; D017366:Serotonin Receptor Agonists