title: Cerebral cation shifts in hypoxic-ischemic brain damage are prevented by the sodium channel blocker tetrodotoxin.
abstract: We investigated the effect of the sodium channel blocker, tetrodotoxin, in two animal models of brain pathology. In the first, an acute model, we recorded the interstitial brain potential in the striatum of rats after cardiac arrest. The time of deflection of this potential, an indication of changes in cerebral cation concentrations, was determined in control rats, and in rats pretreated with intrastriatal tetrodotoxin. In control rats a deflection of the brain potential was noted 2 min after cardiac arrest; tetrodotoxin pretreatment delayed this deflection to about 5 min. The second, a survival model, was based on the Levine preparation in rats. A combination of ischemia and hypoxia produced unilateral, cerebral infarcts, which were characterized by a decrease of brain [K+], and by increases of [Ca2+] and [Na+] and thus of the Na+:K+ ratio. Data on the cation shifts, determined by chemical assay methods, were complemented by those of more conventional methods of assessment of brain damage, such as the determination of survival, of Evans blue staining, and of brain water content. Cation shifts could be prevented locally by tetrodotoxin. In conclusion, the drug can, at least partially, prevent the detrimental effects of an ischemic insult. In addition, our results showed that protective effects observed in the acute model may sometimes offer an indication of the effects to be expected in the survival model. Furthermore, the effect of tetrodotoxin on the brain potentials in the acute model showed that its protective action in the survival model may be brought about by delaying cell depolarization and by shortening the actual duration of the depolarized state. We conclude that Na+ influx and, consequently, neurotransmission may play a crucial role in the development of cerebral damage.
authors.affiliation: Department of Neurosurgery, University of Groningen, University Hospital, The Netherlands.
authors.forename: G H
authors.initials: GH
authors.lastname: Prenen
authors.forename: K G
authors.initials: KG
authors.lastname: Go
authors.forename: F
authors.initials: F
authors.lastname: Postema
authors.forename: F
authors.initials: F
authors.lastname: Zuiderveen
authors.forename: J
authors.initials: J
authors.lastname: Korf
mesh_terms: D000818:Animals; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D005070:Evans Blue / Q000378:metabolism; D005260:Female; D006323:Heart Arrest / Q000139:chemically induced / Q000150:complications; D002534:Hypoxia, Brain / Q000150:complications / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000503:physiopathology*; D008274:Magnesium / Q000378:metabolism; D015636:Magnesium Chloride; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*
chemical_list: D002412:Cations; D015636:Magnesium Chloride; D013779:Tetrodotoxin; D005070:Evans Blue; D012964:Sodium; D008274:Magnesium; D011188:Potassium; D002118:Calcium