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Title: Macrophages and Microglia Produce Local Trophic Gradients That Stimulate Axonal Sprouting Toward but Not beyond the Wound Edge.
Austin Authors: Batchelor, Peter Egerton;Porritt, Michelle J;Martinello, P;Parish, C L;Liberatore, G T;Donnan, Geoffrey A ;Howells, David William
Affiliation: Departments of Medicine, Neurology, The University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia
Issue Date: 1-Nov-2002
Publication information: Molecular and Cellular Neurosciences; 21(3): 436-53
Abstract: Following injury to the mammalian CNS, axons sprout in the vicinity of the wound margin. Growth then ceases and axons fail to cross the lesion site. In this study, using dopaminergic sprouting in the injured striatum as a model system, we have examined the relationship of periwound sprouting fibers to reactive glia and macrophages. In the first week after injury we find that sprouting fibers form intimate relationships with activated microglia as they traverse toward the wound edge. Once at the wound edge, complicated plexuses of fibers form around individual macrophages. Axons, however, fail to grow further into the interior of the wound despite the presence of many macrophages in this location. We find that the expression of BDNF by activated microglia progressively increases as the wound edge is approached, while GDNF expression by macrophages is highest at the immediate wound margin. In contrast, the expression of both factors is substantially reduced within the macrophage-filled interior of the wound. Our data suggest that periwound sprouting fibers grow toward the wound margin along an increasing trophic gradient generated by progressively microglial and macrophage activation. Once at the wound edge, sprouting ceases over macrophages at the point of maximal neurotrophic factor expression and further axonal growth into the relatively poor trophic environment of the wound core fails to occur.
Gov't Doc #: 12498785
Type: Journal Article
Subjects: Animals
Brain Injuries.metabolism.physiopathology
Brain-Derived Neurotrophic Factor.genetics
Dopamine Plasma Membrane Transport Proteins
Glial Cell Line-Derived Neurotrophic Factor
Glial Fibrillary Acidic Protein.metabolism
Growth Cones.metabolism.ultrastructure
Macrophage-1 Antigen.metabolism
Membrane Glycoproteins
Membrane Transport Proteins.metabolism
Mice, Inbred C57BL
Microscopy, Electron
Nerve Growth Factors.genetics.metabolism
Nerve Regeneration.physiology
Nerve Tissue Proteins
Neuronal Plasticity.physiology
RNA, Messenger.metabolism
Wound Healing.physiology
Appears in Collections:Journal articles

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