title: Role of calcium in central nervous system injuries.
abstract: Calcium ions initiate and regulate responses of central nervous tissues to injury. Calcium ions entering injured cells will activate phospholipases, disrupt mitochondrial electron transport, and release free radicals. Neurons normally possess a large reservoir of substances to bind calcium, as well as calcium-activated proteins that protect phospholipids and free radical scavengers. However, calcium entry can initiate a stereotyped injury response. Injured cells release potassium and neurotransmitters that depolarize neighboring cells and cause further calcium entry. Free radical and phospholipase attack of membranes cause lipid peroxidation, generating more free radicals and releasing arachidonic acid. Cyclo-oxygenase and lipo-oxygenase convert arachidonic acid to prostaglandins and leukotrienes, eicosanoids that cause edema and vasoconstriction. Why have neurons, the longest-lived and most important cells of the body, evolved these elaborate autodestructive mechanisms? The calcium-activated injury response may serve a protective purpose. Potassium and neurotransmitter release spreads the calcium load over many cells. Membrane breakdown floods extracellular fluids with phosphates and phosphatides that bind calcium ions. Lowering extracellular calcium activity efficiently reduces the driving force for calcium entry into surviving cells. Edema and vasoconstriction resulting from eicosanoids slow calcium diffusion from blood and surrounding tissues, reducing the probability of "calcium paradox" when calcium returns. The tissue rapidly eliminates moribund cells that would otherwise consume precious metabolic resources. The possibility that the injury response may be protective has important therapeutic implications.
authors.affiliation: Department of Neurosurgery, New York University Medical Center, New York City.
authors.forename: W
authors.initials: W
authors.lastname: Young
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D009474:Neurons / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000503:physiopathology*
chemical_list: D002118:Calcium