Involvement of wound-associated factors in rat brain astrocyte migratory response to axonal injury: in vitro simulation.
The poor ability of mammalian central nervous system (CNS) axons to regenerate has been attributed, in part, to astrocyte behavior after axonal injury. This behavior is manifested by the limited ability of astrocytes to migrate and thus repopulate the injury site. Here, the migratory behavior of astrocytes in response to injury of CNS axons in vivo was simulated in vitro using a scratch-wounded astrocytic monolayer and soluble substances derived from injured rat optic nerves. The soluble substances, applied to the scratch-wounded astrocytes, blocked their migration whereas some known wound-associated factors such as transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and heparin-binding epidermal growth factor in combination with insulin-like growth factor-1 (HB-EGF + IGF-1) stimulated intensive migration with consequent closure of the wound. Migration was not dominated by proliferating cells. Both bFGF and HB-EGF + IGF-1, but not TGF-beta 1, could overcome the blocking effect of the optic nerve-derived substances on astrocyte migration. The induced migration appeared to involve proteoglycans. It is suggestive that appropriate choice of growth factors at the appropriate postinjury period may compensate for the endogenous deficiency in glial supportive factors and/or presence of glial inhibitory factors in the CNS.
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
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Faber-Elman
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Solomon
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Abraham
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Marikovsky
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Schwartz
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000737:chemistry; D002704:Chlorates / Q000494:pharmacology; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D006133:Growth Substances / Q000494:pharmacology*; D019812:Heparan Sulfate Proteoglycans; D019763:Heparin Lyase; D006497:Heparan Sulfate / Q000502:physiology; D009409:Nerve Crush; D009457:Neuroglia / Q000737:chemistry; D009900:Optic Nerve / Q000166:cytology* / Q000502:physiology; D011133:Polysaccharide-Lyases; D011509:Proteoglycans / Q000502:physiology; D051381:Rats; D014945:Wound Healing / Q000502:physiology
D002704:Chlorates; D011508:Chondroitin Sulfate Proteoglycans; D004247:DNA; D005904:Glial Fibrillary Acidic Protein; D006133:Growth Substances; D019812:Heparan Sulfate Proteoglycans; D019763:Heparin Lyase; D006497:Heparan Sulfate; D011133:Polysaccharide-Lyases; D011509:Proteoglycans; C032706:sodium chlorate