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Inhibition of cyclooxygenase-1 does not reduce mortality in post-ischemic stroke rats.

Authors
  • Rostevanov, Ira S1
  • Boyko, Matthew2
  • Ferorelli, Savina3
  • Scilimati, Antonio3
  • Perrone, Maria Grazia3
  • Kaplanski, Jacob1
  • Zlotnik, Alexander2
  • Azab, Abed N4
  • 1 Department of Clinical Biochemistry and Pharmacology, Israel. , (Israel)
  • 2 Department of Anesthesiology and Critical Care, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel. , (Israel)
  • 3 Department of Pharmacy-Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy. , (Italy)
  • 4 Department of Clinical Biochemistry and Pharmacology, Israel; Department of Nursing, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: [email protected] , (Israel)
Type
Published Article
Journal
Neuroscience letters
Publication Date
Oct 15, 2020
Volume
737
Pages
135296–135296
Identifiers
DOI: 10.1016/j.neulet.2020.135296
PMID: 32777346
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Ischemic stroke is one of the leading causes of mortality and morbidity. The currently available non-invasive therapeutic options are not sufficiently efficacious. Post-ischemic brain is characterized by a prominent inflammatory response. Little is known about the involvement of cyclooxygenase (COX)-1 in the pathophysiology of ischemic stroke. This study was undertaken to examine the effects of a highly selective COX-1 inhibitor - mofezolac - on clinical outcomes and brain inflammatory markers in post-stroke rats. Stroke was induced by subjecting rats to permanent middle cerebral artery occlusion (MCAO). Control rats underwent a sham surgery. Rats were treated with mofezolac (50 mg/kg, intraperitoneally [ip]) once daily for 14 days. Control animals were treated with vehicle. Body temperature (BT), neurological score (NS) and cumulative mortality were monitored at different time points. At the end of the experiment, rats were euthanized and three brain regions (hypothalamus, hippocampus and frontal cortex) were extracted. Levels of interleukin (IL)-6, prostaglandin (PG)E2 and tumor necrosis factor (TNF)-α in these brain regions were determined by ELISA kits. BT, NS and cumulative mortality were all significantly higher in post-MCAO rats than in sham-operated rats, irrespective of the treatment given. BT, NS and mortality rate did not differ significantly between mofezolac-treated and vehicle-treated sham-operated animals. BT was significantly lower in mofezolac-treated as compared to vehicle-treated post-MCAO rats. Mofezolac did not significantly alter NS in post-MCAO rats at any time-point. Cumulative 14-day mortality was non-significantly higher in mofezolac-treated as compared to vehicle-treated post-MCAO rats (48 % vs. 21 %, respectively; P = 0.184). Mostly, IL-6 and TNF-α levels did not differ between post-MCAO and sham-operated rats and were not affected by mofezolac treatment. In contrast, mofezolac significantly decreased PGE2 levels in post-MCAO rats' brains. Overall, these results suggest that chronic treatment with the selective COX-1 inhibitor mofezolac did not reduce morbidity or mortality in post-stroke rats. Copyright © 2020 Elsevier B.V. All rights reserved.

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