Acute changes in intermediary metabolism in cerebellum and contralateral hemisphere following middle cerebral artery occlusion in rat.
Focal ischemia leads to functional deafferentation of regions connected to the ischemic area via fiber tracts. Using i.v. administration of 13C-labeled glucose and acetate combined with ex vivo 13C MR spectroscopy and HPLC of brain extracts we identify the effect of middle cerebral artery occlusion (MCAO) on neurotransmitter synthesis and turnover, and on neuro-astrocytic interactions in the non-ischemic cerebellum and in contralesional lateral caudoputamen plus lower parietal cortex (LPC), and upper frontoparietal cortex (UFPCx) in the rat after 30, 60, 120 and 240 min of ischemia. In all regions, there was a significant persisting loss of glutamate, and in LCP and UFPCx also of glutamine, but only in LCP was GABA reduced at all times. Metabolism and blood flow were uncoupled in all regions. In cerebellum, glucose metabolism as well as utilization of intermediates derived from astrocytic tricarboxylic acid cycle activity were significantly decreased at all times in both glutamatergic and GABAergic neurons. In LCP and UFPCx, there were normal or increased enrichment in glutamate and GABA from glucose. Glutamate derived from astrocytic acetate metabolism was increased, but GABA synthesis from acetate was initially impaired. The results showed that both the type of afferent connection, i.e., glutamatergic and/or GABAergic, and local cytoarchitecture, determined the effect MCAO had on metabolic activity in the non-ischemic regions. In conclusion, it was primarily excitatory input into non-ischemic regions that was affected by MCAO, perhaps enabling resetting of the excitatory/inhibitory balance, aiding reshaping of the receptive fields and thus facilitating recovery.
Håberg
Asta K
AK
Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway. asta.haberg@ntnu.no
Qu
Hong
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Sonnewald
Ursula
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D000085:Acetates / Q000378:metabolism; D000208:Acute Disease; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology*; D001253:Astrocytes / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003847:Deoxyglucose; D004594:Electrophysiology; D007839:Functional Laterality / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D020768:Middle Cerebral Artery / Q000473:pathology*; D018377:Neurotransmitter Agents / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D000596:Amino Acids; D018377:Neurotransmitter Agents; D019344:Lactic Acid; D003847:Deoxyglucose; D005947:Glucose