Ischemia and the aging brain — studies on glucose and energy-metabolism in rat cerebral-cortex
Abstract
Age has been considered to be a crucial risk factor for brain ischemic insults and their mortality. Brain ischemia has been found to cause severe abnormalities in glucose metabolism, energy metabolism and related metabolism, thus damaging the structure and function of brain cells. To study the effect of age and ischemia on brain glucose and energy metabolism, investigations were performed on one-and two-year-old male Wistar rats, the latter of which can be designated as aged. In both age groups, ischemia resulted in a depletion of glucose, OAA, ATP AND CRP, a diminution of Pyr, Citr and alpha-Keto and an accumulation of FDP, Lact, Succ, ADP and AMP in brain cortex. During ischemia, differences between the two age groups became most obvious in the concentrations of Glu, FDP, DHAP, Lact, Succ, Mal, ADP and AMP. In general, the metabolic changes in both age groups point to an increased glycolytic flux which may be less accelerated in the aged group, to an inhibition of the starting reactions of the tricarboxylic acid cycle more severe in aged animals, to a preponderance of anaplerotic reactions in this oxidative system more pronounced in the two-year-old group and to a loss of AMP in the same age group. The age-related metabolic variations measured may indicate that with age the biological plasticity of the brain may be reduced to meet emergency conditions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Under aerobic conditions, succinate concentrations in tissues and mitochondria are submillimolar, indicating that complex II does not operate at maximal velocity under standard conditions.
“The succinate concentration in different tissues and mitochondria is in the submillimolar range under aerobic conditions [22,72,73], indicating that complex II is not working at maximal velocity under 'standard conditions'.”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [72]
Cites
Hubert, H. B., Feinleib, M., McNamara, P. M., & Castelli, W. P. (1983) · Circulation · doi:10.1161/01.cir.67.5.968 · Cited by 4,241 · see citing works
A Flexible System of Enzymatic Analysis
Lowry, O. H., & Passonneau, J. V. (1972) · Elsevier eBooks · doi:10.1016/b978-0-12-457950-7.x5001-3 · Cited by 4,050 · see citing works
Energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers
Atkinson, D. (1968) · Biochemistry · doi:10.1021/bi00851a033 · Cited by 2,417 · see citing works
Effect of Ischemia on Known Substrates and Cofactors of the Glycolytic Pathway in Brain
Lowry, O. H., Passonneau, J. V., Hasselberger, F. X., & Schulz, D. W. (1964) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)51740-3 · Cited by 2,222 · see citing works
Cell Damage in the Brain: A Speculative Synthesis
Siesjö, B. K. (1981) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1981.18 · Cited by 1,807 · see citing works
Fuller, J., Shipley, M. J., Rose, G., Jarrett, R. J., & KEEN, H. (1983) · BMJ · doi:10.1136/bmj.287.6396.867 · Cited by 632 · see citing works
Effects of Changes in Brain Metabolism on the Levels of Citric Acid Cycle Intermediates
Goldberg, N. D., Passonneau, J. V., & Lowry, O. H. (1966) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99802-9 · Cited by 396 · see citing works
Barbiturate Protection in Acute Focal Cerebral Ischemia
Smith, A. L., Hoff, J. T., Nielsen, S. L., et al. (1974) · Stroke · doi:10.1161/01.str.5.1.1 · Cited by 371 · see citing works
CEREBRAL CARBOHYDRATE METABOLISM DURING ACUTE HYPOXIA AND RECOVERY1
Duffy, T. E., Nelson, S. B., & Lowry, O. H. (1972) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1972.tb01417.x · Cited by 364 · see citing works
Ljunggren, B., Schutz, H., & Siesjö, B. K. (1974) · Brain Research · doi:10.1016/0006-8993(74)91049-x · Cited by 295 · see citing works
Eolbergrová, J., MacMillan, V., & Siesjö, B. K. (1972) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1972.tb01309.x · Cited by 288 · see citing works
Invertebrate Facultative Anaerobiosis
Hochachka, P. W., & Mustafa, T. (1972) · Science · doi:10.1126/science.178.4065.1056 · Cited by 260 · see citing works
The acute action of ammonia on rat brain metabolism in vivo
Hawkins, R. A., Miller, A. L., Nielsen, R. C., & Veech, R. L. (1973) · Biochemical Journal · doi:10.1042/bj1341001 · Cited by 241 · see citing works
Control of Citric Acid Cycle Activity in Rat Heart Mitochondria
LaNoue, K. F., Nicklas, W. J., & WILLIAMSON, J. R. (1970) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63427-1 · Cited by 227 · see citing works
Energy‐Metabolising Enzymes in Brain Regions of Adult and Aging Rats
Leong, S. F., Lai, J. C. K., Lim, L., & Clark, J. B. (1981) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1981.tb06326.x · Cited by 220 · see citing works
Influence of tissue acidosis upon restitution of brain energy metabolism following total ischemia
Ljunggren, B., Norberg, K., & Siesjö, B. K. (1974) · Brain Research · doi:10.1016/0006-8993(74)90782-3 · Cited by 213 · see citing works
Folbergrová, J., Ljunggren, B., Norberg, K. A., & Siesjö, B. K. (1974) · Brain Research · doi:10.1016/0006-8993(74)90690-8 · Cited by 192 · see citing works
PURINE NUCLEOTIDE METABOLISM IN THE CAT BRAIN AFTER ONE HOUR OF COMPLETE ISCHEMIA
Kleihues, P., Kobayashi, K., & Hossmann, K. ‐. (1974) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1974.tb04374.x · Cited by 183 · see citing works
Brain aging : neuropathology and neuropharmacology
Cervós‐Navarro, J., & Sarkander, H.-I. (1983) · Raven Press eBooks · Cited by 160 · see citing works
Michenfelder, J. D., & Milde, J. H. (1975) · Stroke · doi:10.1161/01.str.6.4.405 · Cited by 146 · see citing works
Abbau freier Nucleotide in Herz, Skeletmuskel, Gehirn und Leber der Ratte bei Sauerstoffmangel
Deüticke, B., & Gerlach, E. (1966) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00362739 · Cited by 144 · see citing works
High-resolution 13C nuclear magnetic resonance studies of glucose metabolism in Escherichia coli.
Uǧurbil, K., Brown, T. R., den Hollander, J. A., Glynn, P., & Shulman, R. G. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.8.3742 · Cited by 141 · see citing works
Facultative Anaerobiosis in the Invertebrates: Pathways and Control Systems
Saz, H. J. (1971) · American Zoologist · doi:10.1093/icb/11.1.125 · Cited by 134 · see citing works
Mitochondrial Response to Transient Forebrain Ischemia and Recirculation in the Rat
Hillered, L., Siesjö, B. K., & Arfors, K. ‐. (1984) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1984.63 · Cited by 127 · see citing works
Mitochondrial metabolism following bilateral cerebral ischemia in the gerbil
Ginsberg, M. D., Mela, L., Wrobel‐Kuhl, K., et al. (1977) · Annals of Neurology · doi:10.1002/ana.410010603 · Cited by 114 · see citing works
The effect of age on glucose and energy metabolism in brain cortex of rats
Hoyer, S. (1985) · Archives of Gerontology and Geriatrics · doi:10.1016/0167-4943(85)90001-9 · Cited by 87 · see citing works
Self-citationAge-dependent Changes in the Oxidative Metabolism in Rat Brain
Patel, M. S. (1977) · Journal of Gerontology · doi:10.1093/geronj/32.6.643 · Cited by 80 · see citing works
Nilsson, L., & Siesjö, B. K. (1970) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1970.tb04787.x · Cited by 72 · see citing works
Furlow, T. W. (1982) · Stroke · doi:10.1161/01.str.13.6.852 · Cited by 70 · see citing works
INFLUENCE OF ANAESTHETICS ON THE BALANCE BETWEEN PRODUCTION AND UTILIZATION OF ENERGY IN THE BRAIN
Nilsson, L., & Siesjö, B. K. (1974) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1974.tb06912.x · Cited by 57 · see citing works
Influence of Nitrous Oxide on Local Cerebral Blood Flow in Awake, Minimally Restrained Rats
Dahlgren, N., Ingvar, M., Yokoyama, H., et al. (1981) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1981.22 · Cited by 54 · see citing works
Haljamäe, H., AMUNDSON, B., BAGGE, U., Jennische, E., & Brånemark, P. (1979) · Pathology - Research and Practice · doi:10.1016/s0344-0338(79)80071-0 · Cited by 52 · see citing works
Peng, M.-T., Peng, Y.-I., & Chen, F.-N. (1977) · Journal of Gerontology · doi:10.1093/geronj/32.5.517 · Cited by 43 · see citing works
Influence of some biological pyrimidines on the succinate cycle during and after cerebral ischemia
Benzi, G. M., Arrigoni, E., Marzatico, F., & Villa, R. F. (1979) · Biochemical Pharmacology · doi:10.1016/0006-2952(79)90024-8 · Cited by 38 · see citing works
Effect of Nitrous Oxide on Local Cerebral Glucose Utilization in Rats
Ingvar, M., & Siesjö, B. K. (1982) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.1982.55 · Cited by 36 · see citing works
The Effect of Halothane Anaesthesia upon Cerebral Oxygen Consumption in the Rat
Harp, J. R., Nilsson, L., & Siesjö, B. K. (1976) · Acta Anaesthesiologica Scandinavica · doi:10.1111/j.1399-6576.1976.tb05013.x · Cited by 24 · see citing works
The Aging Brain: Physiological and Pathophysiological Aspects
(1984) · Journal of Gerontology · doi:10.1093/geronj/39.2.246b · Cited by 20 · see citing works
Glucose and Energy Metabolism of Rat Cerebral Cortex During Aging
Ulfert, G., Schmidt, U., & Høyer, S. (1982) · Experimental brain research. Supplementum · doi:10.1007/978-3-642-68507-1_13 · Cited by 19 · see citing works
Shock : clinical and experimental aspects
LEDINGHAM, I. M. (1976) · Medical Entomology and Zoology · Cited by 18 · see citing works
Heller, M. (1963) · BMJ · doi:10.1136/bmj.2.5361.867-b · Cited by 8 · see citing works
Effects of Aging on Regulation of Cerebral Blood Flow and Metabolism
(1983) · KARGER eBooks · doi:10.1159/isbn.978-3-8055-8781-5 · Cited by 6 · see citing works
Cerebrovascular and Metabolic Response of the Aged Rat to Hypoxia
Hoffman, W. E., Pelligrino, D. A., Miletich, D. J., et al. (2015) · Monographs in clinical neuroscience/Frontiers of neurology and neuroscience/Monographs in neural sciences · doi:10.1159/000409181 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications
Bubber, P., Haroutunian, V., Fisch, G., Blass, J. P., & Gibson, G. E. (2005) · Annals of Neurology · doi:10.1002/ana.20474 · Cited by 622 · see citing works
The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis
Sapieha, P., Sirinyan, M., Hamel, D., Zaniolo, K., Joyal, J.-S., Cho, J.-H., Honoré, J.-C., Kermorvant-Duchemin, E., Varma, D. R., Tremblay, S., et al. (2008) · Nature Medicine · doi:10.1038/nm.1873 · Cited by 359 · see citing works
Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.01.004 · Cited by 201 · see citing works
Siebels, I., & Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.06.005 · Cited by 130 · see citing works
Age as Risk Factor for Sporadic Dementia of the Alzheimer Type?
HOYER, S. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb56833.x · Cited by 38 · see citing works
Self-citationZoccarato, F., Cavallini, L., & Alexandre, A. (2009) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-009-9238-2 · Cited by 31 · see citing works
- Authors
- Hoyer, S., & Krier, C.
- Affiliations
- Heidelberg University (DE)
- Corresponding author
- Hoyer, Siegfried
- ORCID
- Hoyer, Siegfried
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 1986-01
- Volume
- 7
- Issue
- 1
- Pages
- 23-29
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2077227045
- Cited by
- 98
- References
- 42
- Citations by year
- 2024: 1 · 2022: 3 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 4 · 2012: 2
- FWCI
- 3.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- brain aging, cerebral ischemia, glucose metabolism, energy metabolism, cerebral cortex, glycolysis, TCA cycle, anaplerotic reactions, ATP depletion, AMP accumulation
- MeSH terms
- Adenine Nucleotides, Aging, Animals, Cerebral Cortex, Brain Ischemia, Citric Acid Cycle, Energy Metabolism, Glucose, Glycolysis, Male, Rats, Inbred Strains, Succinates, Succinic Acid, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
