Article
5-Lipoxygenase inhibitors alter the spatiotemporal profile of infiltrating macrophages and granulocytes when given prior to experimental traumatic brain injury
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Authors
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Martin U. Schuhmann
- Klinik für Neurochirurgie, Universitätsklinikum Tübingen; Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig
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Dominik Michalski
- Klinik für Neurologie, Universitätsklinikum Leipzig
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Gudrun Seeger
- Paul Flechsig Institut für Hirnforschung, Universität Leipzig
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Cornelia Voigt
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig
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Wolfgang Härtig
- Paul Flechsig Institut für Hirnforschung, Universität Leipzig
| Published: | May 21, 2013 |
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Outline
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Objective: Traumatic brain injury (TBI) typically causes an inflammatory response, which is considered as a significant contributor to neuronal death with consecutive poor outcome. Recently, we showed in a rat model of controlled cortical impact (CCI) that leukotriene inhibitors (LIs) could attenuate contusion growth and improve neuronal survival. The present study focuses on treatment-related spatiotemporal characteristics of macrophages and granulocytes, known to be involved in the inflammatory response, and neuronal cyclooxygenase-2 (COX-2) expression.
Method: Forty rats received CCI and were treated by oral gavage of either vehicle (n=13), MK-886 (n=13) or Boscari (n=14) 2 h prior to injury and every 8 h thereafter. Effects of LIs (Boscari/MK-886) were evaluated by counting immunohistochemically stained CD68+, CD43+ and COX-2+ cells 24 and 72 h post-CCI in pre-defined brain regions: the ipsilateral parietal cortex (PC), CA3 region, dentate gyrus (DG) and visual/auditory cortex (v/aC).
Results: Twenty-four h after CCI, untreated animals showed granulocytes in all regions investigated, decreasing towards 72 h. In contrast, macrophages increased from 24 to 72 h post-CCI in the PC and v/aC. Unexpectedly, COX-2+ neurones showed no temporal changes, except of an increase in the CA3 region towards 72 h. Notably, treatment reduced granulocytes at 24 h in the pericontusional penumbra and hippocampus, and diminished macrophages at 72 h in the PC and v/aC, while COX-2 expression remained unaffected
Conclusions: The beneficial effect of LIs on contusion size and neuronal survival, shown previously in the same model, correlates to the recently observed attenuation of the cellular inflammatory response following CCI. Therefore, the principle of leukotriene inhibition becomes attractive as potential treatment strategy, but further research is warranted to show that a clinical relevant therapeutic window exists for post-trauma treatment and to proof that functional outcome is also improved in treatment groups.
