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Title: Stimulation of axonal sprouting by trophic factors immobilized within the wound core.
Austin Authors: Batchelor, Peter Egerton;Wills, Taryn Elizabeth;Hewa, Ajith Pedru;Porritt, Michelle Julie;Howells, David William
Affiliation: Departments of Medicine and Neurology, University of Melbourne, Austin Health, Heidelberg Victoria 3084, Australia
Issue Date: 10-Mar-2008
Publication information: Brain Research 2008; 1209(): 49-56
Abstract: Traumatic injury to the CNS results in peri-wound sprouting without significant axonal growth beyond the lesion edge. We have previously demonstrated that dopaminergic sprouting in the injured striatum follows an increasing gradient of BDNF and GDNF expression, with sprouting ceasing at the point of maximal factor expression. Progressively more complicated associations of sprouting fibers with increasingly activated microglia and macrophages suggest these factors are localized to the cell surface. To establish whether an increased concentration of immobilized BDNF and GDNF could stimulate axonal growth beyond the lesion edge, both factors were covalently attached to 10 microm polycarbonate microspheres. These spheres were implanted into the site of striatal injury 1 week after lesioning. A profusion of axons grew from the region of the lesion edge across the surface of the spheres. Some axons traversed the entire site of injury. Ultrastructural examination demonstrated the juxtaposition of regenerating axons to the surface of implanted spheres. CSPG immunostaining demonstrated that, in animals implanted with neurotrophin-microspheres, axonal growth was induced beyond the area of maximal CSPG reactivity. Surprisingly however, CSPG production at the wound edge was greater in control animals than those implanted with neurotrophin-microspheres. Overall, we show that axonal growth can be encouraged beyond the wound edge by an elevated concentration of immobilized trophic factors. This growth occurs despite the presence of inhibitory CSPGs at the lesion edge. Axonal growth appears to be stimulated mainly via the direct effects of neurotrophins. However, there also appears to be an indirect mechanism whereby neurotrophins reduce the synthesis of CSPG at the wound edge, making the peri-wound environment more permissive.
Gov't Doc #: 18396265
DOI: 10.1016/j.brainres.2008.02.098
Type: Journal Article
Subjects: Animals
Biological Markers.analysis.metabolism
Brain Injuries.drug therapy.metabolism
Brain-Derived Neurotrophic Factor.pharmacology.therapeutic use
Chondroitin Sulfate Proteoglycans.analysis.metabolism
Disease Models, Animal
Dopamine Plasma Membrane Transport Proteins.analysis.metabolism
Dose-Response Relationship, Drug
Drug Delivery Systems.instrumentation.methods
Glial Cell Line-Derived Neurotrophic Factor.pharmacology.therapeutic use
Growth Cones.drug effects.physiology
Mice, Inbred C57BL
Nerve Growth Factors.pharmacology.therapeutic use
Nerve Regeneration.drug effects.physiology
Neuronal Plasticity.drug effects.physiology
Treatment Outcome
Wound Healing.drug effects.physiology
Appears in Collections:Journal articles

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