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01-04-2017 | Original Article

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

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

Published in: Translational Stroke Research | Issue 2/2017

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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Title: Increased 12/15-Lipoxygenase Leads to Widespread Brain Injury Following Global Cerebral Ischemia
Authors: Kazim Yigitkanli
Yi Zheng
Anton Pekcec
Eng H. Lo
Klaus van Leyen
Publication date: 01-04-2017
Publisher: Springer US
Published in: Translational Stroke Research / Issue 2/2017
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-016-0509-z

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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