title: Perioperative aspirin improves neurological outcome after focal brain ischemia possibly via inhibition of Notch 1 in rat.
abstract: BACKGROUND
  Perioperative discontinuation of aspirin is often considered due to bleeding concern. We determined whether this discontinuation affected neurological outcome after brain ischemia.
  
  
  METHODS
  Adult male Sprague-Dawley rats were subjected to a 90-minute right middle cerebral arterial occlusion (MCAO). They received 30 mg/kg/day aspirin via gastric gavage: 1) for 2 days at 5 days before MCAO; 2) for 2 days at 5 days before MCAO and for 3 days after MCAO; 3) for 7 days before MCAO; or 4) for 7 days before MCAO and for 3 days after MCAO. Neurological outcome was evaluated 3 days after the MCAO. Ischemic penumbral cortex was harvested 1 or 3 days after MCAO for determining Notch intracellular domain (NICD), IL-6 and IL-1β levels.
  
  
  RESULTS
  Aspirin given by regimen 2 and 3 but not by regimen 1 improved neurological outcome. Neuroprotection was achieved by N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a Notch activation inhibitor. DAPT and aspirin given only by regimen 2 and 3 reduced NICD, IL-6 and IL-1β in the ischemic penumbral cortex. NICD was found in microglial nuclei. Microglial activation in the ischemic tissues was inhibited by aspirin.
  
  
  CONCLUSIONS
  Aspirin use during the perioperative period provides neuroprotection. Inhibition of Notch activation and neuroinflammation may contribute to the neuroprotection of aspirin.
authors.forename: Zhongxing
authors.initials: Z
authors.lastname: Wang
authors.forename: Wenqi
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, University of Virginia, 1 Hospital Drive, PO Box 800710, Charlottesville, Virginia 22908-0710, USA. zz3c@virginia.edu.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D004151:Dipeptides / Q000627:therapeutic use; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology*; D011597:Psychomotor Performance / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004151:Dipeptides; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D015850:Interleukin-6; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; D001241:Aspirin