[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.
Adám-Vizi
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Semmelweis Egyetem, Altalános Orvostudományi Kar, Orvosi Biokémia Intézet, Budapest.
D000138:Acidosis / Q000378:metabolism; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015687:Cell Hypoxia / Q000187:drug effects*; D004487:Edema / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014748:Vinca Alkaloids / Q000494:pharmacology*
D000779:Anesthetics, Local; D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; D014748:Vinca Alkaloids; D018698:Glutamic Acid; C013983:vinpocetine; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium