[Neuroprotective effect of sodium channel blockers in ischemia: the pathomechanism of early ischemic dysfunction]

Increase in the intracellular Na+ concentration ([Na+]i) plays a key role in the cell damage induced by ischemia/reperfusion. In addition to imposing an energy demand on cells due to stimulation of the plasmalemmal Na, K-ATPase, it contributes to an impairment of Ca2+ homeostasis by driving Ca2+ into the cells via the Na(+)-Ca2+ exchanger, and to the development of other acute dysfunctions such as acidosis, cytotoxic oedema and glutamate excitotoxicity. Rise is [Na+]i induced by ischemia further worsens during reperfusion when reactive oxygen species are generated, and oxidative stress occurs. As activation of voltage-dependent Na+ channels has a crucial role in mediating a sustained Na+ entry during ischemia, blocking of these channels is expected to exert neuroprotection. Indeed, a wide range of compounds able to block Na+ channels proved to be beneficial in experimental ischemia. Among these are local anaesthetics, Ca2+ channel blockers, anticonvulsants and the neuroprotective drug, vinpocetine.