Serebral İskemi Modelinde Oluşan Nöroinflamasyon Üzerine 12/15 Lipooksijenaz İnhibitörlerinin Etkisi

Abstract

In this study, our aim was to investigate the effect of 12/15 LOX inhibition on neuroinflammation process. For this purpose, two different cerebral ischemia models in mouse, permanent ischemia and ischemia/recanalization (I/R), have been performed. Cerebral ischemia with two different models-induced inflammation and the effects of 12/15 LOX inhibitor on this process were examined at 3 different time points (6, 24 and 72 hours). Blood brain barrier integrity (MMP-9 ve TIMP-1), microglia activation, NLRP1 and NLRP3 inflammasome protein complexes, pro-inflammatory (IL-1beta, IL-6 and TNF-alpha) and anti-inflammatory (TGF-beta and IL-10) cytokines, were observed by immunohistochemistry technique. Moreover, amount of pro-inflammatory and anti-inflammatory cytokines in the brain tissues were investigated by ELISA. Tissue levels of malondialdehyde were assessed to analyze oxidative stress following ischemia. In our results, inflammation process induced by ischemia has different properties according to models and time points of the insult and 12/15 LOX inhibition suppressed inflammatory response in the perienfart region. I/R model was the most suitable model to examine oxidative damage and inflammatory processes after cerebral ischemia and among proinflammatory markers, IL-6 and among anti-inflammatory markers TGF-beta were significantly different in this model. In conclusion, all these findings show that 12/15 LOX inhibition is closely related to the inflammatory process, indicating that it may be an effective target in the treatment of inflammation-induced diseases such as stroke.