Perioperative aspirin improves neurological outcome after focal brain ischemia possibly via inhibition of Notch 1 in rat

Journal of Neuroinflammation

Zhiyi Zuo²  Wenqi Huang¹  Zhongxing Wang¹ 

[1] Department of Anesthesiology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China;Department of Anesthesiology, University of Virginia, 1 Hospital Drive, PO Box 800710, Charlottesville, Virginia 22908-0710, USA

关键词: Notch;    Inflammatory cytokines;    Brain ischemia;    Aspirin;   

Others  :  811718
DOI  :  10.1186/1742-2094-11-56

 received in 2013-09-27, accepted in 2014-03-09,  发布年份 2014

【 摘 要 】

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.

Conclusion

Aspirin use during the perioperative period provides neuroprotection. Inhibition of Notch activation and neuroinflammation may contribute to the neuroprotection of aspirin.

【 授权许可】

   
2014 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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