title: The metabolism of C-glucose by neurons and astrocytes in brain subregions following focal cerebral ischemia in rats.
abstract: To provide insights into the effects of temporary focal ischemia on the function of neurons and astrocytes in vivo, we measured the incorporation of radiolabel from [U-14C]glucose into both glutamate and glutamine in brain subregions at 1 h of reperfusion following occlusion of the middle cerebral artery for 2 or 3 h. Under the experimental conditions used, 14C-glutamate is mainly produced in neurons whereas 14C-glutamine is generated in astrocytes from 14C-glutamate of both neuronal and astrocytic origin. Radiolabel incorporation into both amino acids was greatly decreased. The change in 14C-glutamate accumulation provides strong evidence for substantial reductions in neuronal glucose metabolism. The resulting decrease in delivery of 14C-glutamate from the neurons to astrocytes was probably also the major contributor to the change in 14C-glutamine content. These alterations probably result in part from a marked depression of glycolytic activity in the neurons, as suggested by previous studies assessing deoxyglucose utilization. Alterations in 14C-glucose metabolism were not restricted to tissue that would subsequently become infarcted. Thus, these changes did not inevitably lead to death of the affected cells. The ATP : ADP ratio and phosphocreatine content were essentially preserved during recirculation following 2 h of ischemia and showed at most only moderate losses in some subregions following 3 h of ischemia. This retention of energy reserves despite the decreases in 14C-glucose metabolism in neurons suggests that energy needs were substantially reduced in the post-ischemic brain. Marked increases in tissue lactate accumulation during recirculation, particularly following 3 h of ischemia, provided evidence that impaired pyruvate oxidation probably also contributed to the altered 14C-glucose metabolism. These findings indicate the presence of complex changes in energy metabolism that are likely to greatly influence the responses of neurons and astrocytes to temporary focal ischemia.
authors.affiliation: Centre for Neuroscience and Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, Australia.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Thoren
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Helps
authors.forename: Michael
authors.initials: M
authors.lastname: Nilsson
authors.forename: Neil R
authors.initials: NR
authors.lastname: Sims
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism* / Q000503:physiopathology; D020520:Brain Infarction / Q000378:metabolism / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002250:Carbon Radioisotopes; D002450:Cell Communication / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000096:biosynthesis; D005973:Glutamine / Q000096:biosynthesis; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002250:Carbon Radioisotopes; D005973:Glutamine; D018698:Glutamic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005947:Glucose