title: Artery reopening is required for the neurorestorative effects of angiotensin modulation after experimental stroke.
abstract: BACKGROUND
  Blood flow restoration with fibrinolysis and thrombectomy is recommended to limit injury in stroke patients with proximal artery occlusion. Angiotensin receptor blockers have been shown to be neuroprotective in models of permanent and temporary occlusion, but the benefits on expression of trophic factors have been seen only when the artery is reopened. It is possible that early artery opening with endovascular intervention may increase the likelihood of identifying an effective combination therapy for patients.
  
  
  METHODS
  Normotensive male Wistar rats were subjected to mechanical middle cerebral artery occlusion (either temporary or permanent), followed by randomization to receive candesartan (0.3 mg/kg IV) or saline. Functional outcome, infarct size, and biochemical changes were assessed 24 h after ischemia induction.
  
  
  RESULTS
  Lack of reperfusion blunted candesartan induced neuroprotection (p < 0.05) and reduced the improvement of functional outcome (p < 0.05). With reperfusion, candesartan increased mature BDNF expression in the contralateral hemisphere (p < 0.05) and activated prosurvival (Akt-GSK3-β) signaling (p < 0.05). Without reperfusion, candesartan significantly reduced VEGF expression and MMP activation and increased NOGO A expression, creating an environment hostile to recovery.
  
  
  CONCLUSIONS
  Candesartan induced pro-recovery effects are dependent on the presence of reperfusion.
authors.affiliation: Clinical Pharmacy Department, College of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid, 22110 Jordan.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Alhusban
authors.affiliation: Charlie Norwood VA Medical Center, and Center for Pharmacy and Experimental Therapeutics, University of Georgia College of Pharmacy, and Georgia Regents University, Augusta, GA USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Kozak
authors.affiliation: Charlie Norwood VA Medical Center, and Center for Pharmacy and Experimental Therapeutics, University of Georgia College of Pharmacy, and Georgia Regents University, Augusta, GA USA.
authors.forename: Wael
authors.initials: W
authors.lastname: Eldashan
authors.affiliation: Charlie Norwood VA Medical Center, and Center for Pharmacy and Experimental Therapeutics, University of Georgia College of Pharmacy, and Georgia Regents University, Augusta, GA USA.
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
authors.affiliation: Charlie Norwood VA Medical Center, and Center for Pharmacy and Experimental Therapeutics, University of Georgia College of Pharmacy, and Georgia Regents University, Augusta, GA USA.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
keywords: AT1 blockers; BDNF; Ischemic stroke; Neuroprotection; Reperfusion