caa a22 4500 606215549 CHVBK 20210128101059.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00701-014-2331-2 doi (NATIONALLICENCE)springer-10.1007/s00701-014-2331-2 COX-2 regulation and TUNEL-positive cell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats [Elektronische Daten] [Mattias Günther, Stefan Plantman, Johan Davidsson, Maria Angéria, Tiit Mathiesen, Mårten Risling] 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 24h and 72h 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 72h 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 24h and 72h (p < 0.05). iNOS mRNA was significantly increased in females at 24h (p < 0.05) although protein was not. TUNEL was increased in male rats after 24h (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 24h, 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. Springer-Verlag Wien, 2015 TBI nationallicence COX-2 nationallicence iNOS nationallicence Sex nationallicence Gender nationallicence Secondary inflammation nationallicence Günther Mattias Department of Neuroscience, Experimental Traumatology Unit, Karolinska Institutet, Stockholm, Sweden aut Plantman Stefan Department of Neuroscience, Experimental Traumatology Unit, Karolinska Institutet, Stockholm, Sweden aut Davidsson Johan Division of Vehicle Safety, Department of Applied Mechanics, Chalmers University of technology, Gothenburg, Sweden aut Angéria Maria Department of Neuroscience, Experimental Traumatology Unit, Karolinska Institutet, Stockholm, Sweden aut Mathiesen Tiit Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institutet, Stockholm, Sweden aut Risling Mårten Department of Neuroscience, Experimental Traumatology Unit, Karolinska Institutet, Stockholm, Sweden aut Acta Neurochirurgica Springer Vienna 157/4(2015-04-01), 649-659 0001-6268 157:4<649 2015 157 701 https://doi.org/10.1007/s00701-014-2331-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00701-014-2331-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Günther Mattias Department of Neuroscience, Experimental Traumatology Unit, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Plantman Stefan Department of Neuroscience, Experimental Traumatology Unit, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Davidsson Johan Division of Vehicle Safety, Department of Applied Mechanics, Chalmers University of technology, Gothenburg, Sweden aut NATIONALLICENCE 700 1- Angéria Maria Department of Neuroscience, Experimental Traumatology Unit, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Mathiesen Tiit Department of Clinical Neuroscience, Section of Neurosurgery, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 700 1- Risling Mårten Department of Neuroscience, Experimental Traumatology Unit, Karolinska Institutet, Stockholm, Sweden aut NATIONALLICENCE 773 0- Acta Neurochirurgica Springer Vienna 157/4(2015-04-01), 649-659 0001-6268 157:4<649 2015 157 701