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Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury
Journal article   Open access   Peer reviewed

Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury

Veronica J Tom, Michael P Steinmetz, Jared H Miller, Catherine M Doller and Jerry Silver
The Journal of neuroscience, v 24(29), pp 6531-6539
21 Jul 2004
PMID: 15269264
url
https://doi.org/10.1523/JNEUROSCI.0994-04.2004View
Published, Version of Record (VoR) Open

Abstract

Dextrans - analysis Laminin - pharmacology Cicatrix - etiology Spinal Cord Injuries - complications Ganglia, Spinal - cytology Endocytosis Aggrecans Female Synaptic Vesicles - physiology Tissue Culture Techniques Lectins, C-Type Neuroglia - physiology Extracellular Matrix Proteins - pharmacology Ganglia, Spinal - physiology Rats Nerve Regeneration Rats, Sprague-Dawley Microscopy, Confocal Animals Growth Cones - metabolism Growth Cones - ultrastructure Proteoglycans - pharmacology Growth Cones - drug effects Kinetics Models, Neurological
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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
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