title: Metabolic injury to axons and myelin.
abstract: CNS white matter, the collection of axons and supporting glia of the mammalian CNS, makes up close to 50% of the human brain by volume. Interruption of vital interconnects within this tissue, even over a short segment, often leads to serious morbidity in a broad range of neurological disorders. Axons, glia and myelin express a complex array of conventional voltage gated ion channels, intracellular Ca(2+) release channels, neurotransmitter uptake and release mechanisms, together with matching transmitter receptors. Dysregulation of ion homeostasis induced by injury or energy failure leads to depolarization and intracellular Na(+) accumulation, which in turn triggers inappropriate ion translocation (i.e. Ca(2+) influx) and transmitter release; together these events further promote more Ca(2+) influx, while at the same time triggering even more toxic Ca(2+) release from intracellular Ca(2+) stores. Uncontrolled intracellular Ca(2+) increases overactivate a variety of Ca(2+)-sensitive enzyme systems culminating in permanent injury to axon, myelin and glia.
authors.affiliation: Department of Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, AB, Canada T2N 4N1.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Tsutsui
authors.forename: Peter K
authors.initials: PK
authors.lastname: Stys
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology
chemical_list: D002118:Calcium