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

• Published in: Journal of neuroscience research 2001-12, Vol.66 (5), p.812-820
• Main Authors: Dienel, G A, Liu, K, Cruz, N F
• Format: Article
• Language: English
• Subjects: Acetates - metabolism; Animals; Astrocytes - drug effects; Astrocytes - metabolism; Autoradiography; Bicarbonates - metabolism; Brain Injuries - metabolism; Brain Injuries - physiopathology; Butyrates - metabolism; Carbon Radioisotopes; Cerebral Cortex - cytology; Cerebral Cortex - metabolism; Cerebral Cortex - physiopathology; Citric Acid Cycle - drug effects; Citric Acid Cycle - physiology; Cortical Spreading Depression - drug effects; Cortical Spreading Depression - physiology; Energy Metabolism - drug effects; Energy Metabolism - physiology; Male; Oxidative Phosphorylation - drug effects; Potassium Chloride - pharmacology; Rats; Rats, Sprague-Dawley
• ISSN: 0360-4012
• DOI: 10.1002/jnr.10063

Spreading depression severely disrupts ion homeostasis, causes sensory neglect and motor impairment, and is associated with stroke and migraine. Glucose utilization (CMR(glc)) and lactate production rise during spreading depression, but the metabolic changes in different brain cell types are unknown. Uptake of (14)C-labeled compounds known to be preferentially metabolized by the glial tricarboxylic acid cycle was, therefore, examined during unilateral KCl-induced spreading cortical depression in conscious, normoxic rats. [(14)C]Metabolites derived from [(14)C]butyrate in K+ -treated tissue rose 21% compared to that of untreated contralateral control cortex, whereas incorporation of H(14)CO(3) into metabolites in K+ -treated tissue was reduced to 86% of control. Autoradiographic analysis showed that laminar labeling of cerebral cortex by both (14)C-labeled acetate and butyrate was elevated heterogeneously throughout cortex by an average of 23%; the increase was greatest (approximately 40%) in tissue adjacent to the K+ application site. Local uptake of acetate, butyrate, and deoxyglucose showed similar patterns, and monocarboxylic acid uptake was highest in the structures in which apparent loss of labeled metabolites of [6-(14)C]glucose was greatest. Enhancement of net uptake of acetate and butyrate in cerebral cortex during spreading depression is tentatively ascribed to increased astrocyte metabolism.