Mammalian neurons in the central nervous system are vulnerable to oxygen deprivation. In clinical conditions, such as stroke or apnoea, permanent loss of neuronal functions can occur within minutes of severe hypoxia. 2. Recent studies have focused on the role of Na+ in acute neuronal responses to hypoxia. These studies have shown that the influx of extracellular Na+ is an important factor in hypoxia-induced injury and that blockade of voltage-gated Na+ channels reduces hypoxic responses and injury of neurons. Yet, the mechanism underlying the effect of blockade of Na+ channels on hypoxic injury is unclear. 3. The aim of the present review is to discuss the above topics given the current understanding of the role of Na+ channels in hypoxia and its implications on therapeutic strategy for preventing hypoxia-induced neurological damage. 4. It has been known that the maintenance of ionic homeostasis and membrane properties in neurons are improved by reducing the activity of voltaged-gated Na+ channels during acute hypoxia. 5. Recent studies suggest that persistent Na+ current and Na+-dependent exchangers may play a role in Na+ influx and neuronal injury during hypoxia. 6. The neuroprotective action of blockers of the Na+ channel may also be via the improved maintainance of intracellular energy levels because the action is dependent on cellular energy levels and extracellular glucose during hypoxia. 7. Hence, the blockade of voltage-gated Na+ channels reduces the excitability of neurons, Na+ influx and the accumulation of intracellular Na+. These improve the ionic homeostasis and cellular energy levels and, thus, prevent hypoxia-induced neuronal injury and neuronal damage mediated by Ca2+ overload.
