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Acta Neurochirurgica

, Volume 157, Issue 4, pp 649–659 | Cite as

COX-2 regulation and TUNEL-positive cell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats

  • Mattias Günther
  • Stefan Plantman
  • Johan Davidsson
  • Maria Angéria
  • Tiit Mathiesen
  • Mårten Risling
Experimental research - Brain Injury

Abstract

Introduction

Traumatic brain injury is followed by secondary neuronal degeneration, largely dependent on an inflammatory response. This response is probably gender specific, since females are better protected than males in experimental models. The reasons are not fully known. We examined aspects of the inflammatory response following experimental TBI in male and female rats to explore possible gender differences at 24 h and 72 h after trauma, times of peak histological inflammation and neuronal degeneration.

Methods

A penetrating brain injury model was used to produce penetrating focal TBI in 20 Sprague-Dawley rats, 5 males and 5 females for each time point. After 24 and 72 h the brains were removed and subjected to in situ hybridization and immunohistochemical analyses for COX-2, iNOS, osteopontin, glial fibrillary acidic protein, 3-nitrotyrosine, TUNEL and Fluoro-Jade.

Results

COX-2 mRNA and protein levels were increased in the perilesional area compared to the uninjured contralateral side and significantly higher in males at 24 h and 72 h (p < 0.05). iNOS mRNA was significantly increased in females at 24 h (p < 0.05) although protein was not. TUNEL was increased in male rats after 24 h (p < 0.05). Glial fibrillary acidic protein, osteopontin, 3-nitrotyrosine and Fluoro-Jade stained degenerating neurons were increased in the perilesional area, showing no difference between genders.

Conclusions

COX-2 regulation differed between genders after TBI. The increased COX-2 expression in male rats correlated with increased apoptotic cell death detected by increased TUNEL staining at 24 h, but not with neuronal necrosis measured by Flouro-Jade. Astrogliosis and microgliosis did not differ, confirming a comparable level of trauma. The gender-specific trait of the secondary inflammatory response may be connected to prostaglandin regulation, which may partially explain gender variances in outcome after TBI.

Keywords

TBI COX-2 iNOS Sex Gender Secondary inflammation 

Notes

Acknowledgments

This study was funded by ALF Stockholms Läns Landsting and The Swedish Defense.

Conflicts of interest

All authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Mattias Günther
    • 1
    • 2
  • Stefan Plantman
    • 1
  • Johan Davidsson
    • 3
  • Maria Angéria
    • 1
  • Tiit Mathiesen
    • 4
  • Mårten Risling
    • 1
  1. 1.Department of Neuroscience, Experimental Traumatology UnitKarolinska InstitutetStockholmSweden
  2. 2.Department of Neuroscience, Section of Experimental TraumatologyKarolinska InstitutetStockholmSweden
  3. 3.Division of Vehicle Safety, Department of Applied MechanicsChalmers University of technologyGothenburgSweden
  4. 4.Department of Clinical Neuroscience, Section of NeurosurgeryKarolinska InstitutetStockholmSweden

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