title: Ischemic postconditioning decreases cerebral edema and brain blood barrier disruption caused by relief of carotid stenosis in a rat model of cerebral hypoperfusion.
abstract: OBJECTIVE
  Complications due to brain edema and breakdown of blood brain barrier are an important factor affecting the treatment effects of patients with severe carotid stenosis. In this study, we investigated the protective effects of ischemic postconditioning on brain edema and disruption of blood brain barrier via establishing rat model of hypoperfusion due to severe carotid stenosis.
  
  
  METHODS
  Wistar rat model of hypoperfusion due to severe carotid stenosis was established by binding a stainless microtube to both carotid arteries. Ischemic postconditioning procedure consisted of three cycles of 30 seconds ischemia and 30 seconds reperfusion. Brain edema was evaluated by measuring cerebral water content, and blood brain barrier permeability was assayed by examining cerebral concentration of Evans' Blue (EB) and fluorescein sodium (NaF). ELISA was used to analyze the expression of MMP-9, claudin-5 and occludin. The activity and location of MMP-9 was analyzed by gelatin zymography and in situ zymography, respectively. The distribution of tight junction proteins claudin-5 and occludin was observed by immunohistochemistry.
  
  
  RESULTS
  The increased brain water content and cerebral concentration of EB and NaF were suppressed by administration of ischemic postconditioning prior to relief of carotid stenosis. Zymographic studies showed that MMP-9 was mainly located in the cortex and its activity was significantly improved by relief of carotid stenosis and, but the elevated MMP-9 activity was inhibited markedly by ischemic postconditioning. Immunohistochemistry revealed that ischemic postconditioning improved the discontinuous distribution of claudin-5 and occludin. ELISA detected that the expression of up-regulated MMP-9 and down-regulated claudin-5 and occludin caused by carotid relief were all attenuated by ischemic postconditioning.
  
  
  CONCLUSIONS
  Ischemic postconditioning is an effective method to prevent brain edema and improve BBB permeability and could be used during relief of severe carotid stenosis.
authors.affiliation: Department of Neurosurgery, First Bethune Hospital of Jilin University, Changchun, China.
authors.forename: Fuwei
authors.initials: F
authors.lastname: Yang
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Boyu
authors.initials: B
authors.lastname: Wang
authors.forename: Chuibing
authors.initials: C
authors.lastname: Zhou
authors.forename: Yinan
authors.initials: Y
authors.lastname: Luo
authors.forename: Pengfei
authors.initials: P
authors.lastname: Ge
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001929:Brain Edema / Q000150:complications* / Q000503:physiopathology*; D016893:Carotid Stenosis / Q000150:complications* / Q000628:therapy*; D002560:Cerebrovascular Circulation; D062507:Claudin-5 / Q000378:metabolism; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D057775:Ischemic Postconditioning; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D062793:Occludin / Q000378:metabolism; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar
chemical_list: D062507:Claudin-5; D062793:Occludin; D020780:Matrix Metalloproteinase 9