Novel combinations of ion channel inhibitors for treatment of neurotrauma

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.