title: Effect of a neuronal sodium channel blocker on magnetic resonance derived indices of brain water content during global cerebral ischemia.
abstract: 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 intracellular compartment during cerebral ischemia. Lamotrigine, a neuronal Na(+) channel blocker, has been shown to attenuate the increase in extracellular concentrations of excitatory amino acids (EAA) during ischemia and to improve neurological and histological outcome. Because of its proven ability to reduce EAA levels during ischemia, lamotrigine should also minimize excitotoxic-induced increases in intracellular water content and therefore attenuate changes in the ADC. In this study, we sought to determine the effect of lamotrigine on intra- and extracellular water shifts during transient global cerebral ischemia. Fifteen New Zealand white rabbits were anesthetized and randomized to one of three groups: a control group, a lamotrigine-treated group, or a sham group. After being positioned in the bore of the magnet, a 12-min 50-s period of global cerebral ischemia was induced by inflating a neck tourniquet. During ischemia and early reperfusion there was a similar and significant decrease of the ADC in both the lamotrigine and control group. The ADC in the sham ischemia group remained at baseline throughout the experiment. Lamotrigine-mediated blockade of voltage-gated sodium channels did not prevent the intracellular movement of water during 12 min 50 s of global ischemia, as measured by the ADC, suggesting that the ADC decline may not be mediated by voltage-gated sodium influx and glutamate release.
authors.affiliation: Department of Anesthesiology and General Intensive Care, University of Vienna, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Koinig
authors.forename: J P
authors.initials: JP
authors.lastname: Williams
authors.forename: M J
authors.initials: MJ
authors.lastname: Quast
authors.forename: M H
authors.initials: MH
authors.lastname: Zornow
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001831:Body Temperature; D001834:Body Water / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D000077213:Lamotrigine; D008279:Magnetic Resonance Imaging; D011817:Rabbits; D015424:Reperfusion; D026941:Sodium Channel Blockers; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D026941:Sodium Channel Blockers; D014227:Triazines; D000077213:Lamotrigine