title: Growth-modulating molecules are associated with invading Schwann cells and not astrocytes in human traumatic spinal cord injury.
abstract: 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.
authors.affiliation: Department of Neurology, Aachen University Hospital, Germany. arminbuss@hotmail.com
authors.forename: Armin
authors.initials: A
authors.lastname: Buss
authors.forename: Katrin
authors.initials: K
authors.lastname: Pech
authors.forename: Byron A
authors.initials: BA
authors.lastname: Kakulas
authors.forename: Didier
authors.initials: D
authors.lastname: Martin
authors.forename: Jean
authors.initials: J
authors.lastname: Schoenen
authors.forename: Johannes
authors.initials: J
authors.lastname: Noth
authors.forename: Gary A
authors.initials: GA
authors.lastname: Brook
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000502:physiology*; D001369:Axons / Q000502:physiology; D002921:Cicatrix / Q000503:physiopathology; D024141:Collagen Type IV / Q000502:physiology; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D005455:Fluorescent Antibody Technique / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007797:Laminin / Q000502:physiology; D008875:Middle Aged; D009416:Nerve Regeneration / Q000502:physiology*; D016900:Neurofilament Proteins / Q000502:physiology; D009457:Neuroglia / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000502:physiology; D012583:Schwann Cells / Q000502:physiology*; D013116:Spinal Cord / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*
chemical_list: D024141:Collagen Type IV; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D016900:Neurofilament Proteins; D017475:Receptors, Nerve Growth Factor