title: Novel combinations of ion channel inhibitors for treatment of neurotrauma.
abstract: Neurotrauma results in the progressive degeneration of neurons and glia surrounding the initial injury. Disruptions to myelin structure are a feature of these injuries and are thought to be triggered by excess calcium (Ca2+) influx into myelinating oligodendrocytes and/or their precursor cells. Calcium ions enter oligodendrocytes through a range of receptors including voltage gated calcium channels, N-methyl-D-aspartate (NMDA) receptors, Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and purinergic P2X7 receptors. Inhibitors have been used to limit excess Ca2+ entry following neurotrauma, but clinical success has been limited. We propose that combinations of calcium channel inhibitors may provide an alternative treatment strategy, whereby entry of excess Ca2+ flux through multiple routes is inhibited simultaneously.
authors: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Crawley, Western Australia, 6009, Australia.
authors: Ryan L
authors: RL
authors: O'Hare Doig
authors: Experimental and Regenerative Neurosciences, School of Animal Biology, The University of Western Australia, Crawley, Western Australia, 6009, Australia.
authors: Melinda
authors: M
authors: Fitzgerald
mesh_terms: D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000627:therapeutic use*
chemical_list: D007473:Ion Channels; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D002118:Calcium