title: Heme oxygenase-1 mediated memorial and revivable protective effect of ischemic preconditioning on brain injury.
abstract: OBJECTIVE
  Ischemic preconditioning (IPC) has short-term benefits for stroke patients. However, if IPC protective effect is memorial and the role of the intracellular protective protein heme oxygenase-1 (HO-1) is not known.
  
  
  METHODS
  Ischemic preconditioning and the corresponding sham control were achieved by blocking the blood flow of the left internal carotid artery for 20 min and 2 second, respectively, in rats. Both IPC and sham-operated animals were divided into three groups and treated with PBS, the HO-1 inducer hemin, and the HO-1 inhibitor Znpp. Three weeks after IPC, brain ischemia-reperfusion injury was achieved by left middle cerebral artery obstruction for 45 min followed by 24-h reperfusion.
  
  
  RESULTS
  2,3,5-triphenyltetrazolium chloride staining and neurological dysfunction scoring showed IPC significantly reduced brain infarct area and improved neurological function occurred 3 weeks after IPC. Hemin treatment promoted whereas ZnPP blocked the benefits of IPC. Immunohistochemical analysis and Western blotting showed that the expression of HO-1 was higher in the border zone than in the necrotic core zone. The memorial IPC protection is independent of adenosine receptor A1R and A2aR expressions.
  
  
  CONCLUSIONS
  We found for the first time that the protective effect of IPC can be remembered to protect brain injury occurred after acute response disappear. The results indicate that interventional treatment can achieve protective effect for future cerebral injury not only through interventional treatment itself but also through the memorial and revivable IPC, eliminating the concern that temporary ischemia caused by interventional treatment may leave harmful effect in the brain.
authors.affiliation: Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, Shanghai, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Le
authors.forename: Xue-Yi
authors.initials: XY
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Meng
authors.forename: Qiu-Jun
authors.initials: QJ
authors.lastname: Liang
authors.forename: Xin-Hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Quan
authors.forename: Meng
authors.initials: M
authors.lastname: Xiang
authors.forename: Mei
authors.initials: M
authors.lastname: Jiang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Si-Feng
authors.initials: SF
authors.lastname: Chen
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000150:complications*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008569:Memory Disorders / Q000209:etiology* / Q000517:prevention & control*; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D011524:Protoporphyrins / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011524:Protoporphyrins; D018047:Receptors, Purinergic P1; C028025:protoporphyrin IX; D051547:Heme Oxygenase-1
keywords: Adenosine receptor; Heme oxygenase-1; Ischemic preconditioning; Stroke