title: Matrix metalloproteinases and their inhibitors in human traumatic spinal cord injury.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) are a family of extracellular endopeptidases that degrade the extracellular matrix and other extracellular proteins. Studies in experimental animals demonstrate that MMPs play a number of roles in the detrimental as well as in the beneficial events after spinal cord injury (SCI). In the present correlative investigation, the expression pattern of several MMPs and their inhibitors has been investigated in the human spinal cord.
  
  
  METHODS
  An immunohistochemical investigation in post mortem samples of control and lesioned human spinal cords was performed. All patients with traumatic SCI had been clinically diagnosed as having "complete" injuries and presented lesions of the maceration type.
  
  
  RESULTS
  In the unlesioned human spinal cord, MMP and TIMP immunoreactivity was scarce. After traumatic SCI, a lesion-induced bi-phasic pattern of raised MMP-1 levels could be found with an early up-regulation in macrophages within the lesion epicentre and a later induction in peri-lesional activated astrocytes. There was an early and brief induction of MMP-2 at the lesion core in macrophages. MMP-9 and -12 expression peaked at 24 days after injury and both molecules were mostly expressed in macrophages at the lesion epicentre. Whereas MMP-9 levels rose progressively from 1 week to 3 weeks, there was an isolated peak of MMP-12 expression at 24 days. The post-traumatic distribution of the MMP inhibitors TIMP-1, -2 and -3 was limited. Only occasional TIMP immuno-positive macrophages could be detected at short survival times. The only clear induction was detected for TIMP-3 at survival times of 8 months and 1 year in peri-lesional activated astrocytes.
  
  
  CONCLUSIONS
  The involvement of MMP-1, -2, -9 and -12 has been demonstrated in the post-traumatic events after human SCI. With an expression pattern corresponding largely to prior experimental studies, they were mainly expressed during the first weeks after injury and were most likely involved in the destructive inflammatory events of protein breakdown and phagocytosis carried out by infiltrating neutrophils and macrophages, as well as being involved in enhanced permeability of the blood spinal cord barrier. Similar to animal investigations, the strong induction of MMPs was not accompanied by an expression of their inhibitors, allowing these proteins to exert their effects in the lesioned spinal cord.
authors.affiliation: Department of Neurology, Aachen University Hospital, Aachen, Germany. abuss@ukaachen.de
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 / Q000378:metabolism / Q000473:pathology; D002102:Cadaver; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases