COX-2 Inhibition by Diclofenac Is Associated With Decreased Apoptosis and Lesion Area After Experimental Focal Penetrating Traumatic Brain Injury in Rats
Traumatic brain injury (TBI) is followed by a secondary inflammation in the brain. The inflammatory response includes prostanoid synthesis by the inducible enzyme cyclooxygenase-2 (COX-2). Inhibition of COX-2 is associated with improved functional outcome in experimental TBI models, although central...
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doaj-cfd0c59924054818937066a05aa459482020-11-25T01:26:22ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-07-011010.3389/fneur.2019.00811426481COX-2 Inhibition by Diclofenac Is Associated With Decreased Apoptosis and Lesion Area After Experimental Focal Penetrating Traumatic Brain Injury in RatsKayvan Dehlaghi Jadid0Johan Davidsson1Erik Lidin2Anders Hånell3Maria Angéria4Tiit Mathiesen5Tiit Mathiesen6Mårten Risling7Mattias Günther8Experimental Traumatology Unit, Department of Neuroscience, Karolinska Institutet, Solna, SwedenDivision of Vehicle Safety, Department of Mechanics and Maritime Sciences, Chalmers University of Technology, Gothenburg, SwedenExperimental Traumatology Unit, Department of Neuroscience, Karolinska Institutet, Solna, SwedenExperimental Traumatology Unit, Department of Neuroscience, Karolinska Institutet, Solna, SwedenExperimental Traumatology Unit, Department of Neuroscience, Karolinska Institutet, Solna, SwedenDepartment of Clinical Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkDepartment of Clinical Neuroscience, Karolinska Institutet, Solna, SwedenExperimental Traumatology Unit, Department of Neuroscience, Karolinska Institutet, Solna, SwedenExperimental Traumatology Unit, Department of Neuroscience, Karolinska Institutet, Solna, SwedenTraumatic brain injury (TBI) is followed by a secondary inflammation in the brain. The inflammatory response includes prostanoid synthesis by the inducible enzyme cyclooxygenase-2 (COX-2). Inhibition of COX-2 is associated with improved functional outcome in experimental TBI models, although central nervous system-specific effects are not fully understood. Animal studies report better outcomes in females than males. The exact mechanisms for this gender dichotomy remain unknown. In an initial study we reported increased COX-2 expression in male rats, compared to female, following experimental TBI. It is possible that COX-2 induction is directly associated with increased cell death after TBI. Therefore, we designed a sequential study to investigate the blocking of COX-2 specifically, using the established COX-2 inhibitor diclofenac. Male Sprague-Dawley rats weighing between 250 and 350 g were exposed to focal penetrating TBI and randomly selected for diclofenac treatment (5 μg intralesionally, immediately following TBI) (n = 8), controls (n = 8), sham operation (n = 8), and normal (no manipulation) (n = 4). After 24 h, brains were removed, fresh frozen, cut into 14 μm coronal sections and subjected to COX-2 immunofluorescence, Fluoro Jade, TUNEL, and lesion area analyses. Diclofenac treatment decreased TUNEL staining indicative of apoptosis with a mean change of 54% (p < 0.05) and lesion area with a mean change of 55% (p < 0.005). Neuronal degeneration measured by Fluoro Jade and COX-2 protein expression levels were not affected. In conclusion, COX-2 inhibition by diclofenac was associated with decreased apoptosis and lesion area after focal penetrating TBI and may be of interest for further studies of clinical applications.https://www.frontiersin.org/article/10.3389/fneur.2019.00811/fullcyklooxygenase-2diclofenacfocal penetrating TBINSAIDtraumatic brain injury |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kayvan Dehlaghi Jadid Johan Davidsson Erik Lidin Anders Hånell Maria Angéria Tiit Mathiesen Tiit Mathiesen Mårten Risling Mattias Günther |
spellingShingle |
Kayvan Dehlaghi Jadid Johan Davidsson Erik Lidin Anders Hånell Maria Angéria Tiit Mathiesen Tiit Mathiesen Mårten Risling Mattias Günther COX-2 Inhibition by Diclofenac Is Associated With Decreased Apoptosis and Lesion Area After Experimental Focal Penetrating Traumatic Brain Injury in Rats Frontiers in Neurology cyklooxygenase-2 diclofenac focal penetrating TBI NSAID traumatic brain injury |
author_facet |
Kayvan Dehlaghi Jadid Johan Davidsson Erik Lidin Anders Hånell Maria Angéria Tiit Mathiesen Tiit Mathiesen Mårten Risling Mattias Günther |
author_sort |
Kayvan Dehlaghi Jadid |
title |
COX-2 Inhibition by Diclofenac Is Associated With Decreased Apoptosis and Lesion Area After Experimental Focal Penetrating Traumatic Brain Injury in Rats |
title_short |
COX-2 Inhibition by Diclofenac Is Associated With Decreased Apoptosis and Lesion Area After Experimental Focal Penetrating Traumatic Brain Injury in Rats |
title_full |
COX-2 Inhibition by Diclofenac Is Associated With Decreased Apoptosis and Lesion Area After Experimental Focal Penetrating Traumatic Brain Injury in Rats |
title_fullStr |
COX-2 Inhibition by Diclofenac Is Associated With Decreased Apoptosis and Lesion Area After Experimental Focal Penetrating Traumatic Brain Injury in Rats |
title_full_unstemmed |
COX-2 Inhibition by Diclofenac Is Associated With Decreased Apoptosis and Lesion Area After Experimental Focal Penetrating Traumatic Brain Injury in Rats |
title_sort |
cox-2 inhibition by diclofenac is associated with decreased apoptosis and lesion area after experimental focal penetrating traumatic brain injury in rats |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neurology |
issn |
1664-2295 |
publishDate |
2019-07-01 |
description |
Traumatic brain injury (TBI) is followed by a secondary inflammation in the brain. The inflammatory response includes prostanoid synthesis by the inducible enzyme cyclooxygenase-2 (COX-2). Inhibition of COX-2 is associated with improved functional outcome in experimental TBI models, although central nervous system-specific effects are not fully understood. Animal studies report better outcomes in females than males. The exact mechanisms for this gender dichotomy remain unknown. In an initial study we reported increased COX-2 expression in male rats, compared to female, following experimental TBI. It is possible that COX-2 induction is directly associated with increased cell death after TBI. Therefore, we designed a sequential study to investigate the blocking of COX-2 specifically, using the established COX-2 inhibitor diclofenac. Male Sprague-Dawley rats weighing between 250 and 350 g were exposed to focal penetrating TBI and randomly selected for diclofenac treatment (5 μg intralesionally, immediately following TBI) (n = 8), controls (n = 8), sham operation (n = 8), and normal (no manipulation) (n = 4). After 24 h, brains were removed, fresh frozen, cut into 14 μm coronal sections and subjected to COX-2 immunofluorescence, Fluoro Jade, TUNEL, and lesion area analyses. Diclofenac treatment decreased TUNEL staining indicative of apoptosis with a mean change of 54% (p < 0.05) and lesion area with a mean change of 55% (p < 0.005). Neuronal degeneration measured by Fluoro Jade and COX-2 protein expression levels were not affected. In conclusion, COX-2 inhibition by diclofenac was associated with decreased apoptosis and lesion area after focal penetrating TBI and may be of interest for further studies of clinical applications. |
topic |
cyklooxygenase-2 diclofenac focal penetrating TBI NSAID traumatic brain injury |
url |
https://www.frontiersin.org/article/10.3389/fneur.2019.00811/full |
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