n-(n-(3-5-difluorophenacetyl)alanyl)phenylglycine-tert-butyl-ester and Brain-Infarction

Perioperative discontinuation of aspirin is often considered due to bleeding concern. We determined whether this discontinuation affected neurological outcome after brain ischemia.. 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.. 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.. Aspirin use during the perioperative period provides neuroprotection. Inhibition of Notch activation and neuroinflammation may contribute to the neuroprotection of aspirin.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Brain Infarction; Dipeptides; Disease Models, Animal; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Infarction, Middle Cerebral Artery; Interleukin-1beta; Interleukin-6; Male; Nervous System Diseases; Psychomotor Performance; Rats, Sprague-Dawley; Time Factors