Local uptake of C-14-labeled acetate and butyrate in rat brain in vivo during spreading cortical depression

Spreading depression severely disrupts ion homeostasis, causes sensory negl ect and motor impairment, and is associated with stroke and migraine. Gluco se utilization (CMRglc) and lactate production rise during spreading depres sion, but the metabolic changes in different brain cell types are unknown. Uptake of C-14-labeled compounds known to be preferentially metabolized by the glial tricarboxylic acid cycle was, therefore, examined during unilater al KCI-induced spreading cortical depression in conscious, normoxic rats. [ C-14] Metabolites derived from [C-14]butyrate in K+-treated tissue rose 21 % compared to that of untreated contralateral control cortex, whereas incor poration of (HCO3)-C-14 into metabolites in K+-treated tissue was reduced t o 86% of control. Autoradiographic analysis showed that laminar labeling of cerebral cortex by both C-14-labeled acetate and butyrate was elevated het erogeneously throughout cortex by an average of 23%; the increase was great est (similar to 40%) in tissue adjacent to the K+ application site. Local u ptake of acetate, butyrate, and deoxyglucose showed similar patterns, and m onocarboxylic acid uptake was highest in the structures in which apparent l oss of labeled metabolites of [6-C-14]glucose was greatest. Enhancement of net uptake of acetate and butyrate in cerebral cortex during spreading depr ession is tentatively ascribed to increased astrocyte metabolism. (C) 2001 Wiley-Liss, Inc.