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Cellular and Molecular Determinants of Glial Scar Formation

  • Ann Logan
  • Martin Berry
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 513)

Abstract

Many axotomised neurons die and none of their severed axons regenerate after penetrant CNS injury in the adult. Debris and necrotic tissue is phagacytosed by hematogenous macrophages and microglia. The scar is formed by astrocytes interacting with fibrous tissue invading the wound from the meninges to re-establish the Oa limitans around the margins of a central connective tissue core. Reactive astrocytes and synantocytes and invading meningeal fibroblasts all express axon growth inhibitory ligands within and about the lesion. Severed axons do however regenerate through the wound if stimulated by neurotrophic factors and prevent the deposition of scar tissue. The positive correlation between regeneration and scar failure suggests that neurotrophic factors act to (1) down-regulate receptors for growth inhibitory ligands allowing growth cones to proceed into the wound, and (2) stimulate secretion and release from growth cones of proteases, which actively disperse and inhibit fibrosis. All injury reactive cells in the wound, and the immigrating hematogenous elements, secrete a multitude of cytokines which trophically regulate the sequential development of the scar through acute, subacute and consolidation phases. TGF-ß is probably the initiator of the cascade, and CTGF is its down stream mediator. Administration of recombinant anti-inflammatory compounds, CTGF antagonists, and competitive TGF-ß receptor blockers, and also TGF-ß neutralising antibodies, effectively reduces mesodermal scarring but has little effect on either the glial responses to injury, or axon regeneration. The use of the DNA of some of these anti-scarring agents in gene therapies is also starting to be fruitful, and has advantages over recombinant protein administration.

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Ann Logan
    • 1
  • Martin Berry
    • 2
  1. 1.Molecular NeuroscienceDepartment of MedicineUK
  2. 2.GKT School of Biomedical ResearchCentre for NeuroscienceUK

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