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Neurite Outgrowth Inhibitors in Gliotic Tissue

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The Functional Roles of Glial Cells in Health and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 468))

Abstract

Gliotic tissue is the major obstacle to axon regeneration after CNS injury. We designed tissue culture assays to search for molecules responsible for neurite outgrowth inhibition in gliotic tissue. All the inhibitory activity in injured brain tissue was located in a plasma membrane heparan-sulphate and condroitin-sulphate type-proteoglycan of apparent molecular weight 200kDalton.The proteoglycan core protein (apparent MW 48,000kD) was biologically inactive, whereas the glycosamine-glycan (GAG) chains accounted for the inhibitory activity. Because of its cell location and mode of induction, the inhibitor was called injured membrane proteoglycan, IMP. IMP prevented neurite outgrowth initiation when attached to the culture substrate and caused growth cone collapse when added in solution to neurons with already growing neurites. We concluded that IMP was responsible for preventing injured CNS fibre regeneration. Double-staining immunohistochemistry of normal and gliotic tissue with anti-IMP monoclonal antibodies together with glial and neuronal markers, permitted the unequivocal definition of inhibitor presenting cells by confocal microscopy. IMPimmunostaining in normal CNS was observed exclusively on neurons. However, after a lesion, immunostaining occurred primarily on intensely GFAP-positive reactive astrocytes, but not on OX-42 positive microglia.

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Authors and Affiliations

  1. Neural Plasticity Group, Cajal Institute, 37 Doctor Arce Ave., 28002, Madrid, Spain

    Manuel Nieto-Sampedro

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  1. Manuel Nieto-Sampedro
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Editors and Affiliations

  1. University of Geneva Medical School, Geneva, Switzerland

    Marco Tsacopoulos

  2. Hellenic Pasteur Institute, Athens, Greece

    Rebecca Matsas

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Nieto-Sampedro, M. (1999). Neurite Outgrowth Inhibitors in Gliotic Tissue. In: Matsas, R., Tsacopoulos, M. (eds) The Functional Roles of Glial Cells in Health and Disease. Advances in Experimental Medicine and Biology, vol 468. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4685-6_17

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  • DOI: https://doi.org/10.1007/978-1-4615-4685-6_17

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