Abstract
Most neurodegenerative disorders are insidious with substantial neural injury present well before symptoms are revealed. Thus, at the time of evident disability or impairment, secondary injuries may obscure the inciting neuropathology. This is not true of stroke, where the onset of injury and symptomatology typically coincide. Moreover, there is a distinct and relatively brief temporal pattern of injury. Therefore, models of ischemia/reperfusion can provide significant insight into early and late injuries and the specific mechanisms of each component of injury. Modelling hypoxia and reoxygenation in primary cultures of hippocampal and cortical neurons to examine temporally the source of reactive oxygen species has identified three phases of reactive oxygen species production in hypoxia/reoxygenation. Mitochondria respond first but are quickly limited by the insufficient oxygen. At this point in ischemia, xanthine oxidase becomes an important source of superoxide, whereas during reperfusion NADPH oxidase is a major source of superoxide. This work highlights the value of a model of early and temporally distinct phases of injury and supports the concept that multitarget approaches will be necessary to effectively prevent or reduce neural injury of stroke.
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Milton, R.H., Abramov, A.Y. (2009). Ischemia-Reperfusion Induces ROS Production from Three Distinct Sources. In: Veasey, S. (eds) Oxidative Neural Injury. Contemporary Clinical Neuroscience. Humana Press. https://doi.org/10.1007/978-1-60327-342-8_6
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