ABSTRACT. Excitatory amino acids are increasingly implicated in the pathogenesis of neuronal injury induced by a variety of CNS insults, such as ischemia, trauma, hypoglycemia, and epilepsy. Little is known about the role of amino acids in causing CNS injury in bacterial meningitis. Several amino acids were measured in cerebrospinal fluid and in microdialysis samples from the interstitial fluid of the frontal cortex in a rabbit model of pneumoccocal meningitis. Cerbrospinal fluid concentrations of glutamate, aspartate, glycine, taurine, and alanine increased significantly in infected animals. Among the amino acids with known excitatory or inhibitory function, interstitial fluid concentrations of glutamate were significantly elevated (by 470%).Alanine, a marker for anaerobic glycolysis, also increased in the cortex of infected rabbits. The elevated glutamate concentrations in the brain extracellular space suggest that excitotoxic neuronal injury may play a role in bacterial meningitis. (Pediatr Res 33: 510-513, 1993) Abbreviations CSF, cerebrospinal fluid EAA, excitatory amino acid cfu, colony-forming unit poorly understood. Cerebral blood flow studies in humans and experimental animals with bacterial meningitis suggest that, after an initial hyperemic phase (13), ischemia occurs under certain circumstances and may contribute to the development of neuronal injury (14-16). As with other forms of ischemia-induced CNS injury it is conceivable that the harmful effects of ischemia could be potentiated by EAA during meningitis.A few studies have examined concentrations of amino acids in CSF in bacterial meningitis. A first report in 1975 found increased levels of glutamic acid, glutamine, and y-aminobutyric acid in the CSF of patients with bacterial meningitis (1 7). Other authors have also reported abnormal CSF concentrations of amino acids, but the importance of these changes has not been explored in detail (18)(19)(20). Importantly, it is not known whether amino acid concentrations in the CSF reflect changes occurring in the brain interstitial fluid, the medium relevant for the potential neurotoxicity of EAA. To test the hypothesis that changes in amino acids may play a role in CNS injury during meningitis, we measured in the present study brain interstitial fluid concentrations of several amino acids in a rabbit model of pneumoccoca1 meningitis and determined whether changes similar to those observed in the CSF during meningitis occur in the brain. Interstitial fluid concentrations of amino acids were measured in the cortex because of its proximity to the inflammation in the subarachnoid space and because pathologic changes were primarily found in the cortex in a recent histopathologic study in rats with experimental pneumococcal meningitis (2 1).EAA, physiologic neurotransmitters in the mammalian CNS, are increasingly implicated in the pathogenesis of neuronal injury induced by a variety of CNS insults, such as global and focal ischemia, brain and spinal cord trauma, hypoglycemia, and epilepsy (1-7). There is good...
Metabolic abnormalities during bacterial meningitis include hypoglycorrhachia and cerebrospinal fluid (CSF) lactate accumulation. The mechanisms by which these alterations occur within the central nervous system (CNS) are still incompletely delineated. To determine the evolution of these changes and establish the locus of abnormal metabolism during meningitis, glucose and lactate concentrations in brain interstitial fluid, CSF, and serum were measured simultaneously and sequentially during experimental pneumococcal meningitis in rabbits. Interstitial fluid samples were obtained from the frontal cortex and hippocampus by using in situ brain microdialysis, and serum and CSF were directly sampled. There was an increase of CSF lactate concentration, accompanied by increased local production of lactate in the brain, and a decrease of CSF-to-serum glucose ratio that was paralleled by a decrease in cortical glucose concentration. Brain microdialysate lactate concentration was not affected by either systemic lactic acidosis or artificially elevated CSF lactate concentration. These data support the hypothesis that the brain is a locus for anaerobic glycolysis during meningitis, resulting in increased lactate production and perhaps contributing to decreased tissue glucose concentration.
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