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

• Published in: Brain research Vol. 887; no. 2; pp. 301 - 308
• Main Authors: Koinig, Herbert, Williams, John P., Quast, Michael J., Zornow, Mark H.
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 29.12.2000; Amsterdam Elsevier; New York, NY
• Subjects: amino acids (excitatory); Animals; Biological and medical sciences; Blood Pressure; Body Temperature; Body Water - drug effects; Body Water - physiology; Brain - drug effects; Brain - physiology; Brain - physiopathology; Diffusion-weighted magnetic resonance imaging; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Amino Acids - metabolism; Global cerebral ischemia; Ischemic Attack, Transient - physiopathology; Lamotrigine; Magnetic Resonance Imaging; Medical sciences; Neurology; Rabbits; Reperfusion; Sodium channel blocker; Sodium Channel Blockers; Time Factors; Triazines - pharmacology; Vascular diseases and vascular malformations of the nervous system; Disorders of the nervous system; Sodium channel blocker; Global cerebral ischemia; Diffusion-weighted magnetic resonance imaging; Nervous system diseases; Central nervous system; Rabbit; Cardiovascular disease; Ionic channel; Lagomorpha; Nuclear magnetic resonance imaging; Cerebral disorder; Vascular disease; Vertebrata; Experimental disease; Mammalia; Ischemia; Sodium; Animal; Central nervous system disease; Antagonist; Cerebrovascular disease; Brain (vertebrata)
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)03012-2

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.