«Estudios en el desarrollo y comportamiento del cono de crecimiento distrófico, marca del fracaso en la regeneración en un modelo in vitro de la cicatriz glial y después de la lesión de médula espinal.»
Veronica J. Tom,1 Michael P. Steinmetz,2 Jared H. Miller,1 Catherine M. Doller,1 and Jerry Silver1
1Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, and 2Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio 44106
We have developed a novel in vitro model of the glial scar that mimics the gradient of proteoglycan found in vivo after spinal cord injury. In this model, regenerated axons from adult sensory neurons that extended deeply into the gradient developed bulbous, vacuolated endings that looked remarkably similar to dystrophic endings formed in vivo. We demonstrate that despite their highly abnormal appearance and stalled forward progress, dystrophic endings are extremely dynamic both in vitro and in vivo after spinal cord injury. Time-lapse movies demonstrated that dystrophic endings continually send out membrane veils and endocytose large membrane vesicles at the leading edge, which were then retrogradely transported to the rear of the «growth cone.» This direction of movement is contrary to membrane dynamics that occur during normal neurite outgrowth. As further evidence of this motility, dystrophic endings endocytosed large amounts of dextran both in vitro and in vivo. We now have an in vitro model of the glial scar that may serve as a potent tool for developing and screening potential treatments to help promote regeneration past the lesion in vivo.
The Journal of Neuroscience, July 21, 2004, 24(29):6531-6539; doi:10.1523/JNEUROSCI.0994-04.2004