Regional and temporal variations in the accumulation of unesterified fatty acids and diacylglycerols in the rat brain during kainic acid induced limbic seizures.
These experiments tested the hypothesis that limbic seizures induced by kainic acid (KA) activate mechanisms (e.g. phospholipase) that degrade the cell membrane, causing a release and accumulation of free fatty acids (FFAs) and diacylglycerols (DGs) in brain areas susceptible to seizure-related damage. The possible link between these effects on lipids and the subsequent development of seizure-related brain damage was investigated by studying the temporal and regional relationship between alterations in lipids in the hippocampus, frontal cerebral cortex, amygdala, striatum and cerebellum, and the development and severity of seizures. Rats were treated with 10 mg/kg KA (s.c.) and sacrificed by head focused microwave irradiation at 1 h, 2 h, 24 h, or 7 days. Levels of FFAs and DGs were determined by gas liquid chromatography (GLC). Brain regions from control rats differed markedly in the content and composition of both FFA and DG pools. Changes in FFAs and DGs during KA-induced limbic seizures also varied from region to region and over time after drug treatment. The largest increases in FFAs in amygdala, striatum, cortex and hippocampus occurred during the peak of seizure activity. Although DG levels were altered in some areas at some time points, there was no apparent correlation between changes in DGs and seizure severity. However, increases in DGs occurred at later time points, coincident with the occurrence of neuronal cell loss in amygdala, cortex, hippocampus and striatum. These data indicate that limbic seizures activate the accumulation of FFAs through increased neuronal activity, while accumulation of DGs may be related to the development of seizure-related brain damage.
Birkle
D L
DL
Department of Pharmacology & Toxicology, West Virginia University, Morgantown 26506-9223.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002849:Chromatography, Gas; D004075:Diglycerides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D007608:Kainic Acid; D008032:Limbic System / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D013997:Time Factors
D004075:Diglycerides; D005230:Fatty Acids, Nonesterified; D007608:Kainic Acid