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

Abstract

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.

Glucose and lactate metabolism during brain activation

“…3; Dienel et al, 2000). During spreading depression, the maximal increases in acetate uptake were even higher, about 40%, and the pattern of increased acetate labeling in the tissue surrounding the KCl application site and the dorsal and ventral layers of cerebral cortex resembled that of [ Dienel et al, 2001b). Thus, enhanced acetate uptake in vivo tentatively indicates that astrocytic oxidative metabolism is increased during normal physiological stimulation and that the stimulation may be especially pronounced during a pathophysiologic condition such as spreading depression.…”

Spreading Depression, Spreading Depolarizations, and the Cerebral Vasculature

“…Stimulation-induced rises in cerebral metabolic rate of O 2 (CMRO 2 ) are controlled by the ATP turnover, which depends on the energy used to fuel the Na ϩ -K ϩ -ATPase to reestablish ionic gradients after SD (110,111). Therefore, SD-induced rises in CMRO 2 support the increased Na ϩ -K ϩ -ATPase activity (42, 68,69,75,143,146,258,262,298,320,364,433,440). The huge rise in cytosolic Ca 2ϩ after SD depolarizes neuronal mitochondria and may trigger a rise in CMRO 2 via the Ca 2ϩ uniporter in the inner mitochondrial membrane (536).…”

The Astrocyte: Powerhouse and Recycling Center

“…Resolution at cell level is now possible using cell-specific labeled compounds, such as acetate, which is unambiguously taken up by astrocytes (Waniewski and Martin 1998). Apart from chromatographic separation of metabolites from lysates and, subsequently, scintillation counting, [ 14 C]-labeled acetate has frequently been used together with autoradiography to map astrocytic metabolism (Muir et al 1986;Dienel et al 2001). On the basis of this method, an activity-dependent regulation of oxidative metabolism in astrocytes has been shown (Cruz et al 2005), which was later replicated using the PET-tracer [1-…”