title: Either brain-derived neurotrophic factor or neurotrophin-3 only neurotrophin-producing grafts promote locomotor recovery in untrained spinalized cats.
abstract: Background. Transplants of cellular grafts expressing a combination of 2 neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been shown to promote and enhance locomotor recovery in untrained spinalized cats. Based on the time course of recovery and the absence of axonal growth through the transplants, we hypothesized that recovery was due to neurotrophin-mediated plasticity within the existing locomotor circuitry of the lumbar cord. Since BDNF and NT-3 have different effects on axonal sprouting and synaptic connectivity/strengthening, it becomes important to ascertain the contribution of each individual neurotrophins to recovery. Objective. We studied whether BDNF or NT-3 only producing cellular grafts would be equally effective at restoring locomotion in untrained spinal cats. Methods. Rat fibroblasts secreting one of the 2 neurotrophins were grafted into the T12 spinal transection site of adult cats. Four cats in each group (BDNF alone or NT-3 alone) were evaluated. Locomotor recovery was tested on a treadmill at 3 and 5 weeks post-transection/grafting. Results. Animals in both groups were capable of plantar weight-bearing stepping at speed up to 0.8 m/s as early as 3 weeks and locomotor capabilities were similar at 3 and 5 weeks for both types of graft. Conclusions. Even without locomotor training, either BDNF or NT-3 only producing grafts promote locomotor recovery in complete spinal animals. More clinically applicable delivery methods need to be developed.
authors.affiliation: PPD France SAS, Ivry sur Seine, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Ollivier-Lanvin
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Itzhak
authors.initials: I
authors.lastname: Fischer
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Tom
authors.affiliation: Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Houlé
authors.affiliation: Temple University, Philadelphia, PA, USA mlemay@temple.edu.
authors.forename: Michel A
authors.initials: MA
authors.lastname: Lemay
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000627:therapeutic use*; D002415:Cats; D004195:Disease Models, Animal; D005080:Exercise Test; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000637:transplantation*; D008124:Locomotion; D020933:Neurotrophin 3 / Q000378:metabolism / Q000627:therapeutic use*; D020127:Recovery of Function / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020933:Neurotrophin 3
keywords: kinematics; locomotion; neurotrophin; plasticity; spinal cord injury