Calcium dyshomeostasis in white matter pathology

Calcium (Ca2+) dyshomeostasis is a major event in the pathophysiology of white matter disorders of the brain and spinal cord. All cellular components of white matter, including macroglial cells and axons, are endowed with membrane Ca2+-permeable receptors and channels lodged in the cell membrane, as well as store-operated channels and pumps. Intracellular Ca2+ overload resulting from deregulated activity of channels, such as those opened by glutamate and ATP, is deleterious to glia and axons. In this review, I summarize recent advances in our understanding of white matter Ca2+ dyshomeostasis in experimental paradigms which are relevant to stroke, perinatal ischemia, multiple sclerosis, psychiatric disorders, Alzheimer's disease and traumatic injury, and discuss some of the clinical implications of these findings.