title: Distinct roles for metalloproteinases during traumatic brain injury.
abstract: Significant protease activations have been reported after traumatic brain injury (TBI). These proteases are responsible for cleavage of transmembrane proteins in neurons, glial, and endothelial cells and this results in the release of their extracellular domains (ectodomains).
  
  
  
  Two TBI models were employed here, representing both closed head injury (CHI) and open head injury (OHI). In situ zymography, immunohistochemistry, bright field and confocal microscopy, quantification of immunopositive cells and statistical analysis were applied.
  
  
  
  We found, using in situ zymography, that gelatinase activity of matrix metalloproteinases (MMP)-2 and MMP-9 was upregulated in cortex of both injury models. Using immunohistochemistry for several MPPs (Matrix metalloproteinases) and ADAMs (disintegrin and metalloproteinases), including MMP-2, -9, ADAM-10, -17, distinct patterns of induction were observed in the two TBI models. In closed head injury, an early increase in protein expression of MMP-2, -9 and ADAM-17 was found as early as 10 min post injury in cortex and peaked at 1 h for all 4 proteases examined. In contrast, after OHI the maximal expression was observed locally neighboring the impact site, at a later time-point, as long as 24 h after the injury for MMP-2 and MMP-9. Confocal microscopy revealed colocalization of the 4 proteases with the neuronal marker NeuN in CHI, but only MMP2 colocalized with NeuN in OHI.
  
  
  
  The findings may lead to a trauma-induced therapeutic strategy triggered soon after a primary insult to improve survival and to reduce brain damage following TBI.
authors.affiliation: Brain Research Center, University of British Columbia, Vancouver, BC, Canada. Electronic address: zhang.si@hotmail.com.
authors.forename: Si
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Brain Research Center, University of British Columbia, Vancouver, BC, Canada. Electronic address: lkojic@mail.ubc.ca.
authors.forename: Luba
authors.initials: L
authors.lastname: Kojic
authors.affiliation: Brain Research Center, University of British Columbia, Vancouver, BC, Canada. Electronic address: myt1@sfu.ca.
authors.forename: Michelle
authors.initials: M
authors.lastname: Tsang
authors.affiliation: Brain Research Center, University of British Columbia, Vancouver, BC, Canada. Electronic address: parampal.grewal@gmail.com.
authors.forename: Parampal
authors.initials: P
authors.lastname: Grewal
authors.affiliation: International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada. Electronic address: jliu@icord.org.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: dnamjoshi@cmmt.ubc.ca.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Namjoshi
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: cheryl@cmmt.ubc.ca.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Wellington
authors.affiliation: International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC, Canada. Electronic address: tetzlaff@icord.org.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Tetzlaff
authors.affiliation: Brain Research Center, University of British Columbia, Vancouver, BC, Canada. Electronic address: cynader@brain.ubc.ca.
authors.forename: Max S
authors.initials: MS
authors.lastname: Cynader
authors.affiliation: Brain Research Center, University of British Columbia, Vancouver, BC, Canada. Electronic address: w.jia@ubc.ca.
authors.forename: William
authors.initials: W
authors.lastname: Jia
mesh_terms: D000072198:ADAM17 Protein / Q000502:physiology; D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000201:enzymology / Q000473:pathology; D006259:Craniocerebral Trauma / Q000201:enzymology* / Q000473:pathology; D016489:Head Injuries, Closed / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000072198:ADAM17 Protein
keywords: Closed and open head injury; Gelatinase activity; Immunohistochemistry; Metalloproteinases; Mice model; Traumatic brain injury