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J Neurophysiol (July 25, 2007). doi:10.1152/jn.00391.2007
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Submitted on April 5, 2007
Accepted on July 25, 2007

Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats

Vanessa Susanne Boyce1, Maureen A Tumolo1, Itzhak Fischer1, Marion Murray1, and Michel A Lemay1*

1 Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States

* To whom correspondence should be addressed. E-mail: michel.lemay{at}drexelmed.edu.

In spinal cats, locomotor recovery without rehabilitation is limited, but weight-bearing stepping returns with treadmill training. We investigated whether neurotrophins administered to the injury-site also restores locomotion in untrained spinal cats, and whether combining both neurotrophins and training further improves recovery. Ordinary rat fibroblasts or a mixture of fibroblasts secreting Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) (Fb-NTF) were grafted into T12 spinal transection sites. Cats with each transplant type were divided into two groups: one trained daily and the other not trained. As expected, trained cats with/without neurotrophin-producing transplants stepped on the treadmill. Untrained cats without neurotrophin-producing transplants could not locomote. However, untrained cats with neurotrophin-secreting transplants performed plantar weight bearing stepping at speeds up to 0.8 m/s as early as 2 weeks post-transection. Locomotor capability and stance lengths in these animals were similar to those in animals receiving training alone suggesting that BDNF/NT-3 administration was equivalent to treadmill training in restoring locomotion in chronically spinalized cats. Cats receiving both interventions showed the greatest improvement in step length. Anatomical evaluation indicated that all transections were complete and that axons did not enter the cord caudal to the graft. Thus, BDNF/NT-3 secreting fibroblasts were equivalent to training in their ability to engage the locomotor circuitry in chronic spinal cats. Furthermore, the rapid time-course of recovery and absence of axonal growth through the transplants indicate that the restorative mechanisms were not related to supraspinal axonal growth. Finally, the results show that transplants beneficial in rodents are applicable to larger mammals.




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R. D. de Leon
Could Neurotrophins Replace Treadmill Training as Locomotor Therapy Following Spinal Cord Injury? Focus on "Neurotrophic Factors Promote and Enhance Locomotor Recovery in Untrained Spinalized Cats"
J Neurophysiol, October 1, 2007; 98(4): 1845 - 1846.
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