Effect of a neuronal sodium channel blocker on magnetic resonance derived indices of brain water content during global cerebral ischemia

Diffusion-weighted magnetic resonance imaging (DWI) with calculation of the apparent diffusion coefficient (ADC) of water is a widely used noninvasive method to measure movement of water from the extracellular to the intracel lular compartment during cerebral ischemia. Lamotrigine. a neuronal Na+ cha nnel blocker, has been shown to attenuate the increase in extracellular con centrations of excitatory amino acids (EAA) during ischemia and to improve neurological and histological outcome. Because of its proven ability to red uce EAA levels during ischemia, lamotrigine should also minimize excitotoxi c-induced increases in intracellular water content and therefore attenuate changes in the ADC. In this study, we sought to determine the effect of lam otrigine on intra- and extracellular water shifts during transient global c erebral ischemia. Fifteen New Zealand white rabbits were anesthetized and r andomized to one of three groups: a control group, a lamotrigine-treated gr oup, or a sham group. After being positioned in the bore of the magnet, a 1 2-min 50-s period of global cerebral ischemia was induced by inflating a ne ck tourniquet.. During ischemia and early reperfusion there was a similar a nd significant decrease of the ADC in both the lamotrigine and control grou p, The ADC in the sham ischemia group remained at baseline throughout the e xperiment. Lamotrigine-mediated blockade of voltage-gated sodium channels d id not prevent the intracellular movement of water during 12 min 50 s of gl obal ischemia, as measured by the ADC, suggesting that the ADC decline may not be mediated by voltage-gated sodium influx and glutamate release. (C) 2 000 Elsevier Science BN. All rights reserved.