Rapid shrinkage of rat striatal extracellular space after local kainate application and ischemia as recorded by impedance.
Early changes in tissue extracellular space following exposure to the excitotoxin kainate in the striatum were compared to those following cardiac arrest of rats anesthetized by chloral hydrate. Tissue extracellular space was monitored by impedance measurements. The possible role of voltage-sensitive Na channels and energy metabolism was studied by local and systemic application of tetrodotoxine (TTX) and glucose, respectively. After both kainate intoxication and cardiac arrest the extracellular space (normally about 20%) became less than one-half within 15 min. TTX caused a delay in the effect of cardiac arrest, and a slight attenuation of that of kainate. Glucose was ineffective in both preparations. Parallel to a decrease in the extracellular space whole tissue Na/K ratio increased. These experiments show that excitotoxins and cardiac arrest cause similar (and not additive) changes in the extracellular space and that these changes are not mediated by Na channels. In cardiac arrest the onset of the extracellular space alterations is triggered by Na+ influx, thus presumably by neurotransmitter release. It is suggested that most (if not all) currently described protective measures against ischemic, hypoxic, or hypoglycemic brain damage are based on a prolongation of the time of onset leading to cell depolarization, rather than suppressing damaging processes during depolarization.
Korf
J
J
Department of Biological Psychiatry, University Psychiatric Clinic, Groningen, The Netherlands.
Postema
F
F
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D004558:Electric Stimulation; D005110:Extracellular Space / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D013779:Tetrodotoxin; D007608:Kainic Acid