Experimental Global Ischemia and White Matter Injury

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White matter injury has been increasingly recognized as an important part of several CNS diseases including brain ischemia. However, compared to mechanisms of neuronal cell death in gray matter, white matter pathophysiology remains relatively understudied and poorly understood. This is especially true in the research field of global ischemia. In both experimental animals and humans, transient global cerebral ischemia leads to delayed cell death in selectively vulnerable brain areas, such as hippocampus, striatum, and the layers 3, 5, and 6 in cortex. Thus far, most efforts in this field have focused on understanding the mechanisms of neuronal cell death, especially in hippocampal CA1 region. However, studies using whole-animal and cell culture models of global ischemia have shown key mechanisms of white matter damage after the injury. In this chapter, we overview those rodent models of global ischemia and, then, try to summarize the current knowledge about the white matter pathophysiology. Similar to stroke or head injury, white matter damage by global cerebral ischemia, such as cardiac arrest, remains a major cause of permanent disability. Hence, a deeper understanding of pathophysiology of white matter injury after global cerebral ischemia may eventually lead us to new therapeutic targets for patients suffering from a wide range of white matter-related diseases.