Abstract
The most important early pathomechanism in traumatic brain injury (TBI) is alteration of the resting membrane potential. This may be mediated via voltage, or agonist-dependent ion channels (e.g. glutamate-dependent channels). This may result in a consequent increase in metabolism with increased oxygen consumption, in order to try to restore ionic balance via the ATP-dependent pumps. We hypothesize that glutamate is an important agonist in this process and may induce an increase in lactate, potassium and brain tissue C02, and hence a decrease in brain pH. Further we propose that an increase in lactate is thus not an indicator of anaerobic metabolic conditions as has been thought for many years.
We therefore analyzed a total of 85 patients with TBI, Glasgow Coma Scale (GCS) < 8 using microdialysis, brain tissue oxygen, C02 and pH monitoring. Cerebral blood flow studies (CBF) were performed to test the relationship between regional cerebral blood flow (rCBF) and the metabolic determinants.
Glutamate was significantly correlated with lactate (p < 0.0001), potassium (p < 0.0001), brain tissue pH (p = 0.0005), and brain tissue C02 (p = 0.006). rCBF was inversely correlated with glutamate, lactate and potassium. 44% of high lactate values were observed in brain with tissue oxygen values, above the threshold level for cell damage.
These results support the hypothesis of a glutamate driven increase in metabolism, with secondary traumatic depolarization and possi- bly hyperglycolysis. Further, we demonstrate evidence for lactate production in aerobic conditions in humans after TBI. Finally, when reduced regional cerebral blood flow (rCBF) is observed, high dialysate glutamate, lactate and potassium values are usually seen, suggesting ischemia worsens these TBI-induced changes.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Andersen B, Marmarou A (1992) Post-traumatic selective stimulation of glycolisis. Brain Res 585(1–2): 184–189
Bergsneider M, Hovda D, Shalmon E, Kelly D, Vespa P, MArtin N, Phelps M, McArthur D, Caron M, Kraus J, Becker D (1997) Cerebral hyperglycolisis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg 86(2): 241–251
Bittar P, Charnay Y, Pellerin L, Bouras C, Magistretti P (1996) Selective distribution of lactate dehydrogenase isoenzymes in neurons and astrocytes of human brain. J Cereb Blood Flow Metab 16: 1079
Friberg H, Ferrand-Drake M, Bengtsson F, Halestrap A, Wieloch T (1998) Cyclosporin A, but not FK 506, protects mitochondria and neurons against hypoglycemic damage and implicates the mitochondrial permeability transition in cell death. J Neurosci 18(4): 5151–5159
Katayama Y, Becker D, Tamura T, Hovda D (1990) Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neuro- surg 73(6): 889–900
Katayama Y, Maeda T, Koshinaga M, Kawamata T, Tsubokawa T (1995) Role of excitatory amino acid-mediated ionic fluxes in traumatic brain injury. Brain Pathol 5(4): 427–435
Larrabee M (1995) Lactate metabolism and its effect on glucose metabolism in an excised neural tissue. J Neurochem 64: 1734–1741
Larrabee M (1996) Partitioning of C02 production between glucose and lactate in excised sympathetic ganglia with implications for brain. J Neurochem 67: 1726–1734
Levasseur J, Alessandri B, Reinert M, Bullock M, Povlishock J, Kontos H (1999) Fluid percussion injury transiently increases then decreases brain oxygen consumption in the rat. J Neurotrauma (in submission)
Li P, Uchino H, Elmer E, Siesjo B (1997) Amelioration by Cyclosporin A of brain damage following 5 or 10 min of ische- mia in rats subjected to preischemic hyperglycemia. Brain Res 753: 133–140
Magistretti P, Sorg O, Yu N, MArtin J, Pellerin L (1993) Neurotransmitters regulate energy metabolism in astrocytes: implications for the metabolic trafficking between neural cells. Dev Neurosci 15: 306–312
Magistretti P, Pellerin L, Rothman D, Shulman R (1999) Energy on demand. Science 283: 495–497
Maran A, Cranston I, Macdonald I, Amiel S (1994) Protection by lactate of cerebral function during hypoglycemia. Lancet 343: 16
Mayevsky A, Manor T, Meilin S, Doron A, Ouankine G (1998) Real-time multiparametric monitroing of the injured human cerebral cortex- a new approach. Acta Neurochir [Suppl] (Wien) 71:78–81
Obrenovitch T, Urenjak J (1997) Is high extracellular glutamate the key to excitotxicity in traumatic brain injury. J Neurotrauma 14(10): 677–698
Pellerin L, Magistretti P (1994) Glutamate uptake into astrocytes stimulates aerobic glycolisis: A mechanism coupling neuronal activity to glucose utilization. Neurobiology 91(22): 10625–10629
Pellerin L, Pellegri G, Bittar P, Charnay Y, Bouras C, Stella N, Magistretti P (1998) Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Develop- ment Neurosci 20: 291–299
Schousboe A, Westergaard N, Waagepetersen H, Larsson O, Bakken I, Sonnewald U (1997) Trafficking between glia and neurons of TCA cycle intermediates and related metabolites. Glia 21: 99–105
Schurr A, West C, Rigor B (1988) Lactate supported synaptic function in the rat hippocampal slice preparation. Science 240: 1326–1328
Schurr A, Miller J, Payne R, Rigor B (1999) An increase in lactate output by brain tissue serves to meet the energy needs of glutamate-activated neurons. J Neurosci 19(1): 34–39
Tomita Y, Stiefel M, Marmarou A (1999) Ionic dysfunction accompanying traumatic brain injury in rats. Poster program, American Association of Neurological Surgeons. Poster 1417: 239
Tscaopoulos M, Magistretti P (1996) Metabolic coupling between Glia and Neurons. J Neurosci 16(3): 877–885
Valadka A, Goodman J, Gopinath S, Uzura M, Robertson C (1998) Comparison of brain tissue oxygen tension to microdialysis-based measures of cerebral ischemia in fatally head injured patients. J Neurotrauma 15(7): 509–519
Vega C, Poitry-Yamate C, Jirounek P, Tsacopoulos M, Coles J (1998) Lactate is released and taken up by isolated rabit vagus nerve during aerobic metabolism. J Neurochem 71(1): 330–337
Waagepetersen H, Bakken I, Larsson O, Sonnewald U, Schousboe A (1998) Metabolism of lactate in cultured GABAergic neurons studied by 13C nuclear magnetic resonance spectroscopy. J Cereb Blood Flow Metab 18(1): 109–117
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2000 Springer-Verlag Wien
About this paper
Cite this paper
Reinert, M., Hoelper, B., Doppenberg, E., Zauner, A., Bullock, R. (2000). Substrate Delivery and Ionic Balance Disturbance After Severe Human Head Injury. In: Mendelow, A.D., et al. Brain Edema XI. Acta Neurochirurgica Supplements, vol 76. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6346-7_91
Download citation
DOI: https://doi.org/10.1007/978-3-7091-6346-7_91
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-7257-5
Online ISBN: 978-3-7091-6346-7
eBook Packages: Springer Book Archive