Inhibiting 12/15-lipoxygenase to treat acute stroke in permanent and tPA induced thrombolysis models

Brain Research
H KaratasK van Leyen

Abstract

12/15-Lipoxygenase (12/15-LOX) contributes to the brain damage after middle cerebral artery occlusion (MCAO) in the acute phase of stroke. The aim of this study was to investigate the effects of a 12/15-LOX inhibitor, LOXBlock-1(LB1), in mice using a FeCl3-induced permanent distal MCAO model and FeCl3-induced ischemia/thrombolysis with tPA. In order to induce permanent distal MCAO, 30% FeCl3 was used in C57BL6 mice. LB1 or DMSO treatments were applied intraperitoneally 2 h following MCAO. For FeCl3-induced ischemia/thrombolysis experiments, 10% FeCl3 was preferred so as to obtain reperfusion with tPA in CD1 mice. 4 h following ischemia either LB1 or DMSO and iv tPA was administered. Outcomes were NSS, weight loss, infarct volume, hemorrhage area and reperfusion rate. FeCl3-induced distal MCAO caused an increase in 12/15-LOX signal in the ischemic cortex with an increase in MDA2 and AIF immunoreactivity. LB1 treatment, applied 2 h after ischemia, significantly decreased the infarct volume at 24 h of permanent distal MCAO. Weight loss was also significantly reduced in LB1 treated group. Distal MCAO and tPA application with LB1 or DMSO showed that treatment significantly decreased the infarct volume and the hemorrhage area. The re...Continue Reading

Citations

Aug 14, 2020·Neural Regeneration Research·Franziska LieschkeKlaus van Leyen
Aug 28, 2020·Frontiers in Neuroscience·Xu SheBiao Tang
Apr 18, 2020·International Immunology·Akari NakamuraTakashi Shichita
Jan 25, 2021·Neuroscience Letters·Min-Yi YaoJing Gao
Nov 5, 2019·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Marjann SchäferHartmut Kuhn
Nov 3, 2020·Frontiers in Cellular Neuroscience·Jie LiuYi Yang
Apr 4, 2020·Cell Chemical Biology·Rajiv R Ratan
Jun 22, 2021·Frontiers in Cellular Neuroscience·Yongfa ZhangTao Li

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