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Erschienen in: Translational Stroke Research 2/2017

12.11.2016 | Original Article

Increased 12/15-Lipoxygenase Leads to Widespread Brain Injury Following Global Cerebral Ischemia

verfasst von: Kazim Yigitkanli, Yi Zheng, Anton Pekcec, Eng H. Lo, Klaus van Leyen

Erschienen in: Translational Stroke Research | Ausgabe 2/2017

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Abstract

Global ischemia following cardiac arrest is characterized by high mortality and significant neurological deficits in long-term survivors. Its mechanisms of neuronal cell death have only partially been elucidated. 12/15-lipoxygenase (12/15-LOX) is a major contributor to delayed neuronal cell death and vascular injury in experimental stroke, but a possible role in brain injury following global ischemia has to date not been investigated. Using a mouse bilateral occlusion model of transient global ischemia which produced surprisingly widespread injury to cortex, striatum, and hippocampus, we show here that 12/15-LOX is increased in a time-dependent manner in the vasculature and neurons of both cortex and hippocampus. Furthermore, 12/15-LOX co-localized with apoptosis-inducing factor (AIF), a mediator of non-caspase-related apoptosis in the cortex. In contrast, caspase-3 activation was more prevalent in the hippocampus. 12/15-lipoxygenase knockout mice were protected against global cerebral ischemia compared to wild-type mice, accompanied by reduced neurologic impairment. The lipoxygenase inhibitor LOXBlock-1 similarly reduced neuronal cell death both when pre-administered and when given at a therapeutically relevant time point 1 h after onset of ischemia. These findings suggest a pivotal role for 12/15-LOX in both caspase-dependent and caspase-independent apoptotic pathways following global cerebral ischemia and suggest a novel therapeutic approach to reduce brain injury following cardiac arrest.
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Metadaten
Titel
Increased 12/15-Lipoxygenase Leads to Widespread Brain Injury Following Global Cerebral Ischemia
verfasst von
Kazim Yigitkanli
Yi Zheng
Anton Pekcec
Eng H. Lo
Klaus van Leyen
Publikationsdatum
12.11.2016
Verlag
Springer US
Erschienen in
Translational Stroke Research / Ausgabe 2/2017
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI
https://doi.org/10.1007/s12975-016-0509-z

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