Impact of 5-lipoxygenase inhibitors on the spatiotemporal distribution of inflammatory cells and neuronal COX-2 expression following experimental traumatic brain injury in rats

Inflammation induced by traumatic brain injury (TBI) is considered as contributor to neuronal death with poor outcome. Although anti-inflammatory strategies were beneficial in experimental TBI, clinical translations mostly failed, probably caused by the complexity of involved cells and mediators. We recently showed in a rat model of controlled cortical impact (CCI) that leukotriene inhibitors (LIs) attenuate contusion growth and improve neuronal survival. This study focuses on spatiotemporal characteristics of macrophages and granulocytes, typically involved in inflammatory processes, and neuronal COX-2 expression. Further, effects of LIs (Boscari/MK-886) were evaluated by quantifying CD68+, CD43+ and COX-2+ cells 24 and 72 h post-CCI in the parietal cortex (PC), CA3 region (CA3r), dentate gyrus (DG) and visual/auditory cortex (v/aC). Correlations were applied to identify inter-cellular relationships. At 24 h, 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. COX-2+ neurones showed no temporal dynamics, except of an increase in the CA3r towards 72 h. Treatment reduced granulocytes at 24 h in the pericontusional penumbra and hippocampus, and reduced macrophages at 72 h in the PC and v/aC. COX-2 expression remained unaffected by LIs, except of time-specific reactions in the DG (increase/decrease at 24/72 h). Interrelations confirmed concomitant cellular reactions beyond initial trauma site. In conclusion, LIs attenuated the cellular inflammatory response following CCI and therefore become attractive as potential treatment strategy. Future studies should clarify region-specific effects and feasible time windows for applying LIs after CCI.