title: Immunohistochemical analysis of TIMP-2 and collagen types I and IV in experimental spinal cord ischemia-reperfusion injury in rats.
abstract: BACKGROUND
  Thoracic and thoracoabdominal aortic intervention carries a significant risk of spinal cord ischemia. The pathophysiologic mechanisms that cause hypoxic/ischemic injury to the spinal cord have not been totally explained. In normal spinal cord, neurons and glial cells do not express type IV collagen. Type IV collagen produced by reactive astrocytes is reported to participate in glial scar formation. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors that regulate the activity of the matrix metalloproteinases (MMPs). TIMP-2 binds strongly with MMP-2, facilitating activation by membrane-type MMP. Imbalance between TIMPs and MMPs can lead to excessive degradation of matrix components. Type IV collagen involved in the blood-brain barrier disruption and glial scar formation, TIMP-2 influences MMP-2 that controls degradation of collagen I and IV.
  
  
  OBJECTIVE
  To examine the immunohistochemical analysis of TIMP-2 and collagen types I-IV in experimental spinal cord ischemia-reperfusion in rats.
  
  
  METHODS
  Thirty-two male Wistar rats weighing 250-300 g were divided into four groups: group S: sham group (n = 8); group 0P: 30-minute occlusion without perfusion (n = 8); group 3P: 30-minute occlusion and 3-hour perfusion (n = 8); and group 24P: 30-minute occlusion and 24-hour perfusion (n = 8). Infrarenal aorta was cross-clamped at two sites by using two aneurysm clips for 30 minutes. Reperfusion was provided after removal of the clips. Lumbar spinal cord segments were removed for immunohistochemical analysis.
  
  
  RESULTS
  TIMP-2 and collagen staining in 3-hour perfused (3P) group were nearly the same with sham group (S). TIMP-2 and collagen staining increased in the 24-hour perfused group.
  
  
  CONCLUSIONS
  Alterations in collagen levels may relate to the biphasic breakdown of the blood-brain barrier and collagen staining in new cell types with relation to glial scar formation. Our results demonstrate that 3-hour perfusion after occlusion in hypoxic/ischemic spinal cord injury seems to be the critical reversible period.
authors.affiliation: Department of Neurosurgery, School of Medicine, University of Kocaeli, Turkey. drianik@gmail.com
authors.forename: Ihsan
authors.initials: I
authors.lastname: Anik
authors.forename: Sibel
authors.initials: S
authors.lastname: Kokturk
authors.forename: Hamza
authors.initials: H
authors.lastname: Genc
authors.forename: Burak
authors.initials: B
authors.lastname: Cabuk
authors.forename: Kenan
authors.initials: K
authors.lastname: Koc
authors.forename: Sadan
authors.initials: S
authors.lastname: Yavuz
authors.forename: Sureyya
authors.initials: S
authors.lastname: Ceylan
authors.forename: Savas
authors.initials: S
authors.lastname: Ceylan
authors.forename: Levent
authors.initials: L
authors.lastname: Kamaci
authors.forename: Yonca
authors.initials: Y
authors.lastname: Anik
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism*; D024141:Collagen Type IV / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion / Q000009:adverse effects; D013116:Spinal Cord / Q000378:metabolism*; D020760:Spinal Cord Ischemia / Q000473:pathology*; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D019716:Tissue Inhibitor of Metalloproteinase-2