COX-2 inhibition by diclofenac is associated with decreased apoptosis and lesion area after experimental focal penetrating traumatic brain injury in rats
Journal article, 2019

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 ?g 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?m 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.

cyklooxygenase-2

NSAID

Focal penetrating TBI

Diclofenac

Traumatic brain injury

Author

Kayvan Dehlaghi Jadid

Karolinska Institutet

Johan Davidsson

Injury Prevention

Erik Lidin

Karolinska Institutet

Anders Hanell

Karolinska Institutet

Maria Angeria

Karolinska Institutet

T. Mathiesen

Rigshospitalet

Karolinska Institutet

M Risling

Karolinska Institutet

Mattias Günther

Karolinska Institutet

Frontiers in Neurology

1664-2295 (ISSN)

Vol. 10 July 811

Subject Categories

Other Clinical Medicine

Neurosciences

Pharmacology and Toxicology

DOI

10.3389/fneur.2019.00811

More information

Latest update

10/16/2019