Brain metabolism of exogenous pyruvate

González, Susana Villa; Nguyen, Nga H.T.; Rise, Frode; Hassel, Bjørnar

doi:10.1111/j.1471-4159.2005.03365.x

Cited by 67 publications

(71 citation statements)

References 44 publications

(97 reference statements)

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“…Its elevation in the brain signals cerebral ischemic damage. 30 However, lactate and pyruvate can readily cross the blood-brain barrier and enter the tricarboxylic acid cycle, 31,32 being preferential oxidative energy substrates over glucose for neurons. 33,34 The beneficial effect of exogenous glucose, lactate, and pyruvate has been shown in some TBI models, [35][36][37] but these substrates only modestly reduce the lesion size, with no apparent functional protection in our model.…”

Section: Discussionmentioning

confidence: 99%

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Dong

Zhang

Hamblin

et al. 2015

J Cereb Blood Flow Metab

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Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energyproducing insufficient tissue-like injured brain.

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Section: Discussionmentioning

confidence: 99%

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Dong

Zhang

Hamblin

et al. 2015

J Cereb Blood Flow Metab

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“…Amino acids were analyzed by high-performance liquid chromatography (HPLC) and fluorescence detection after precolumn derivatization with o-phthaldialdehyde, using an 1100 series HPLC unit (Agilent), as described previously. 9 Supernatants of brain abscess pus were analyzed by reflectance spectrophotometry for glucose and lactate as described previously, 17 and pH was measured with a pH meter (inoLab pH 7110, WTW GmbH) that was calibrated before each reading.…”

Section: Biochemical Analysesmentioning

confidence: 99%

Toxic levels of ammonia in human brain abscess

Dahlberg¹,

Ivanović²,

Hassel

2016

JNS

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obJective Brain abscesses could lead to cerebral symptoms through tissue destruction, edema, changes in brain architecture, and increased intracranial pressure. However, the possibility that the pus itself could contribute to symptoms has received little attention. Brain abscesses are areas of tissue destruction, proteolysis, and formation of free amino acids, which are energy substrates for bacteria and possible sources of ammonia. Ammonia is neurotoxic, may cause brain edema, and could contribute to the symptoms of brain abscesses. methods The authors analyzed the extracellular phase of pus from 14 patients with brain abscesses with respect to ammonia and amino acids. For comparison, CSF from 10 patients undergoing external ventricular drainage was included. The ammonia-forming ability of Streptococcus intermedius and Staphylococcus aureus, two common microbial isolates in brain abscesses, was studied in vitro. results In brain abscesses ammonia was 15.5 mmol/L (median value; range 1.7-69.2 mmol/L). In CSF ammonia was 29 µmol/L (range 17-55 µmol/L; difference from value in pus: p < 0.001). The total concentration of amino acids in brain abscesses was 1.12-16 times higher than the ammonia concentration (p = 0.011). The median glucose value in pus was 0 mmol/L (range 0-2.1 mmol/L), lactate was 21 mmol/L (range 3.3-26.5 mmol/L), and pH was 6.8 (range 6.2-7.3). In vitro, S. intermedius and S. aureus formed ammonia at 6-7 mmol/L in 24 hours when incubated with 20 proteinogenic amino acids plus g-aminobutyric acid (GABA), taurine, and glutathione at 1 mmol/L. coNclusioNs Intracerebral abscesses contain toxic levels of ammonia. At the concentrations found in pus, ammonia could contribute to the brain edema and the symptoms of brain abscesses.

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“…It has been shown that overexpression of MnSOD, 0.5-2 fold, can attenuate kainate induced seizures, however animals with diminished MnSOD levels showed an exacerbation of kainate-induced seizure and hippocampal damage, which was attenuated with antioxidant treatment (Patel, 2002). Overexpression of MnSOD also produces lower amounts of inactive aconitase and 8-hydroxy-2-deoxyguanosine (8-OHdG), measures of oxidative protein and DNA (most likely mtDNA) damage, indicating a role in the preservation of mitochondrial function (Gonzalez, et al, 2005, Patel, 2002, Sleven, et al, 2006. Damage to mitochondrial complex I, α-keto-glutarate dehydrogenase, citrate synthase, aconitase, and GSH can be detected at time points well after the end of an epileptic episode, and damage to these cellular components can induce cell death cascades and increase the likelihood of future seizures .…”

Section: Antioxidative Mechanismsmentioning

confidence: 99%