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Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats
Journal article   Open access   Peer reviewed

Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats

Vanessa S Boyce, Maureen Tumolo, Itzhak Fischer, Marion Murray and Michel A Lemay
Journal of neurophysiology, v 98(4), pp 1988-1996
Oct 2007
DOI: https://doi.org/10.1152/jn.00391.2007
PMID: 17652412
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1152/jn.00391.2007View
Published, Version of Record (VoR) Open

Abstract

Immunohistochemistry Decerebrate State - physiopathology Cats Data Interpretation, Statistical Fibroblasts - transplantation Decerebrate State - drug therapy Hindlimb - physiology Neuronal Plasticity - drug effects Decerebrate State - therapy Exercise Therapy Nerve Growth Factors - pharmacology Biomechanical Phenomena Brain-Derived Neurotrophic Factor - pharmacology Animals Neuronal Plasticity - physiology Fibroblasts - drug effects Female Functional Laterality - physiology Spinal Cord - cytology Locomotion - physiology Neurotrophin 3 - pharmacology
In spinal cats, locomotor recovery without rehabilitation is limited, but weight-bearing stepping returns with treadmill training. We studied 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 type of transplant were divided into two groups: one receiving daily training and the other receiving no training. As expected, trained cats with/without neurotrophin-producing transplants could step 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 wk after transection. Locomotor capability and stance lengths in these animals were similar to those in animals receiving training alone, suggesting that administration of BDNF/NT-3 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 the 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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Web of Science research areas
Neurosciences
Physiology
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