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Excess glutamate in the cerebrospinal fluid in bacterial meningitis
M Spranger1, S Krempien, S Schwab
1Department of Neurology, University of Heidelberg, Germany.
Abstract:
We investigated possible neurotoxic components in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. On murine cerebellar neuronal cell cultures, CSF exerted a dose-dependent toxic effect, which was attenuated by the NMDA receptor antagonist MK-801. Glutamate concentrations in the CSF of patients with bacterial meningitis were measured by an enzymatic assay and found to be significantly elevated (p < 0.001) as compared to viral meningitis and non-inflammatory neurological diseases. The concentration of glutamate in the CSF of patients with bacterial meningitis varied considerably and correlated with the severity of the disease as scored by the Glasgow Coma Scale. Cells in the CSF, mainly comprising polymorphonuclear granulocytes, did not release any glutamate into the culture medium, whereas blood monocytes produced remarkable amounts. These findings implicate an important role of monocytic inflammatory cells in bacterial meningitis by the release of glutamate, which may contribute to neuronal cell death.
Insights
Elevated glutamate in cerebrospinal fluid (CSF) from bacterial meningitis patients contributes to neurotoxicity. Monocytes release glutamate, potentially causing neuronal cell death in this condition.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Bacterial meningitis can lead to severe neurological complications.
- The exact neurotoxic mechanisms in bacterial meningitis are not fully understood.
Purpose of the Study:
- To investigate neurotoxic components in cerebrospinal fluid (CSF) from bacterial meningitis patients.
- To identify the role of glutamate and inflammatory cells in meningitis-associated neurotoxicity.
Main Methods:
- Murine cerebellar neuronal cell cultures were exposed to CSF.
- Glutamate concentrations in CSF were measured using an enzymatic assay.
- Glutamate release from CSF cells and blood monocytes was assessed.
Main Results:
- CSF from bacterial meningitis patients induced dose-dependent neurotoxicity, reduced by NMDA receptor antagonist MK-801.
- Glutamate levels were significantly elevated in bacterial meningitis CSF compared to viral meningitis and non-inflammatory controls.
- CSF glutamate concentration correlated with disease severity (Glasgow Coma Scale).
- Blood monocytes, but not CSF polymorphonuclear granulocytes, released significant amounts of glutamate.
Conclusions:
- Glutamate is a key neurotoxic component in the CSF of bacterial meningitis patients.
- Monocytic inflammatory cells play a significant role in bacterial meningitis by releasing glutamate.
- Glutamate release by monocytes may contribute to neuronal cell death in bacterial meningitis.