Toxic levels of ammonia in human brain abscess.

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.

[1]  E. C. Murphy,et al.  Gram-positive anaerobic cocci--commensals and opportunistic pathogens. , 2013, FEMS microbiology reviews.

[2]  J. Ivanović,et al.  High extracellular concentration of excitatory amino acids glutamate and aspartate in human brain abscess , 2014, Neurochemistry International.

[3]  D. Beighton,et al.  Emended descriptions and recognition of Streptococcus constellatus, Streptococcus intermedius, and Streptococcus anginosus as distinct species. , 1991, International journal of systematic bacteriology.

[4]  J. Häberle Abstracts from the Conference Clinical and biochemical aspects of primary and secondary hyperammonemic disorders. , 2022, Folia neuropathologica.

[5]  V. Crow,et al.  Arginine metabolism in lactic streptococci , 1982, Journal of bacteriology.

[6]  M. Kilian,et al.  Reclassification of Actinobacillus actinomycetemcomitans, Haemophilus aphrophilus, Haemophilus paraphrophilus and Haemophilus segnis as Aggregatibacter actinomycetemcomitans gen. nov., comb. nov., Aggregatibacter aphrophilus comb. nov. and Aggregatibacter segnis comb. nov., and emended description o , 2006, International journal of systematic and evolutionary microbiology.

[7]  M. Brouwer,et al.  Clinical characteristics and outcome of brain abscess , 2014, Neurology.

[8]  W. Lo,et al.  Blood-brain barrier permeability in staphylococcal cerebritis and early brain abscess. , 1994, Journal of neurosurgery.

[9]  G. Auzinger,et al.  Arterial ammonia and clinical risk factors for encephalopathy and intracranial hypertension in acute liver failure , 2007, Hepatology.

[10]  W. Jacobson,et al.  The two types of nucleoproteins during mitosis , 1952 .

[11]  C. W. Moss,et al.  Cultural Characteristics and Fatty Acid Composition of Corynebacterium acnes , 1967, Journal of bacteriology.

[12]  D. Straus,et al.  Growth and Amino Acid Requirements of Various Strains of Group B Streptococci , 1978, Journal of clinical microbiology.

[13]  C. Vance,et al.  Granule Localization of Glutaminase in Human Neutrophils and the Consequence of Glutamine Utilization for Neutrophil Activity* , 2004, Journal of Biological Chemistry.

[14]  M. Sakamoto,et al.  Prevotella shahii sp. nov. and Prevotella salivae sp. nov., isolated from the human oral cavity. , 2004, International journal of systematic and evolutionary microbiology.

[15]  A. Crane,et al.  Damage to Neurons in Culture Following Medium Change: Role of Glutamine and Extracellular Generation of Glutamate , 1993, Journal of neurochemistry.

[16]  D. Hoffmann,et al.  Necrotic tumor versus brain abscess: importance of amino acids detected at 1H MR spectroscopy--initial results. , 1999, Radiology.

[17]  J. Russell,et al.  Transport of glutamine by Streptococcus bovis and conversion of glutamine to pyroglutamic acid and ammonia , 1989, Journal of bacteriology.

[18]  D. Krieger,et al.  Correlation Between Ammonia Levels and the Severity of Hepatic Encephalopathy , 2004 .

[19]  O. Vanderkooi,et al.  The significance of Streptococcus anginosus group in intracranial complications of pediatric rhinosinusitis. , 2013, JAMA otolaryngology-- head & neck surgery.

[20]  Jingyu Chen,et al.  Metabolic profiling of Staphylococcus aureus cultivated under aerobic and anaerobic conditions with (1)H NMR-based nontargeted analysis. , 2012, Canadian journal of microbiology.

[21]  F. Rise,et al.  Brain metabolism of exogenous pyruvate , 2005, Journal of neurochemistry.

[22]  F. Schliess,et al.  Osmotic and oxidative/nitrosative stress in ammonia toxicity and hepatic encephalopathy. , 2013, Archives of biochemistry and biophysics.

[23]  S. Gharbia,et al.  Fusobacterium nucleatum subsp. fusiforme subsp. nov. and Fusobacterium nucleatum subsp. animalis subsp. nov. as additional subspecies within Fusobacterium nucleatum. , 1992, International journal of systematic bacteriology.

[24]  Thomas Zeuthen,et al.  Ammonia and urea permeability of mammalian aquaporins. , 2009, Handbook of experimental pharmacology.

[25]  Maiken Nedergaard,et al.  Ammonia triggers neuronal disinhibition and seizures by impairing astrocyte potassium buffering , 2013, Nature Medicine.

[26]  M. Norenberg,et al.  Brain edema in acute liver failure: mechanisms and concepts , 2014, Metabolic Brain Disease.

[27]  E. Alpern,et al.  Abscess Volume and Ultrasound Characteristics of Community-Associated Methicillin-Resistant Staphylococcus aureus Infection , 2013, Pediatric emergency care.

[28]  P. Pohl,et al.  Permeation of ammonia across bilayer lipid membranes studied by ammonium ion selective microelectrodes. , 1997, Biophysical journal.

[29]  R. Butterworth,et al.  Neurobiology of ammonia , 2002, Progress in Neurobiology.

[30]  R. Hurley,et al.  Inactivation of penicillin by purulent exudates. , 1977, British medical journal.

[31]  K. Wanner,et al.  Deletion of the γ-Aminobutyric Acid Transporter 2 (GAT2 and SLC6A13) Gene in Mice Leads to Changes in Liver and Brain Taurine Contents* , 2012, The Journal of Biological Chemistry.

[32]  R. Britt,et al.  Neuropathological and computerized tomographic findings in experimental brain abscess. , 1981, Journal of neurosurgery.

[33]  C. Gips,et al.  Determination of ammonia in cerebrospinal fluid using the indophenol direct method. , 1998, Molecular and chemical neuropathology.

[34]  J. Díaz,et al.  Reference intervals for blood ammonia in healthy subjects, determined by microdiffusion. , 1995, Clinical chemistry.

[35]  Sajja B Rao,et al.  Brain abscesses: etiologic categorization with in vivo proton MR spectroscopy. , 2004, Radiology.

[36]  Arthur J. L. Cooper,et al.  The Role of Glutamine Synthetase and Glutamate Dehydrogenase in Cerebral Ammonia Homeostasis , 2012, Neurochemical Research.

[37]  À. Rovira,et al.  MR Imaging Findings in Hepatic Encephalopathy , 2008, American Journal of Neuroradiology.

[38]  T. R. Oberhofer,et al.  Biotypes of Haemophilus encountered in clinical laboratories , 1979, Journal of clinical microbiology.

[39]  Y. Izumi,et al.  Ammonia inhibits long-term potentiation via neurosteroid synthesis in hippocampal pyramidal neurons , 2013, Neuroscience.