Journal Article

Growth-modulating molecules are associated with invading Schwann cells and not astrocytes in human traumatic spinal cord injury

Armin Buss, Katrin Pech, Byron A. Kakulas, Didier Martin, Jean Schoenen, Johannes Noth and Gary A. Brook

in Brain

Published on behalf of The Guarantors of Brain

Volume 130, issue 4, pages 940-953
Published in print April 2007 | ISSN: 0006-8950
Published online February 2007 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awl374
Growth-modulating molecules are associated with invading Schwann cells and not astrocytes in human traumatic spinal cord injury

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Despite considerable progress in recent years, the underlying mechanisms responsible for the failure of axonal regeneration after spinal cord injury (SCI) remain only partially understood. Experimental data have demonstrated that a major impediment to the outgrowth of severed axons is the scar tissue that finally dominates the lesion site and, in severe injuries, is comprised of connective tissue and fluid-filled cysts, surrounded by a dense astroglial scar. Reactive astrocytes and infiltrating cells, such as fibroblasts, produce a dense extracellular matrix (ECM) that represents a physical and molecular barrier to axon regeneration. In the human situation, correlative data on the molecular composition of the scar tissue that forms following traumatic SCI is scarce. A detailed investigation on the expression of putative growth-inhibitory and growth-promoting molecules was therefore performed in samples of post-mortem human spinal cord, taken from patients who died following severe traumatic SCI. The lesion-induced scar could be subdivided into a Schwann cell dominated domain which contained large neuromas and a surrounding dense ECM, and a well delineated astroglial scar that isolated the Schwann cell/ECM rich territories from the intact spinal parenchyma. The axon growth-modulating molecules collagen IV, laminin and fibronectin were all present in the post-traumatic scar tissue. These molecules were almost exclusively found in the Schwann cell-rich domain which had an apparent growth-promoting effect on PNS axons. In the astrocytic domain, these molecules were restricted to blood vessel walls without a co-localization with the few regenerating CNS neurites located in this region. Taken together, these results favour the notion that it is the astroglial compartment that plays a dominant role in preventing CNS axon regeneration. The failure to demonstrate any collagen IV, laminin or fibronectin upregulation associated with the astroglial scar suggests that other molecules may play a more significant role in preventing axon regeneration following human SCI.

Keywords: spinal cord injury; human; regeneration; glial scar

Journal Article.  8761 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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