Related Experiment Video
Updated: Jun 8, 2026
Non-Invasive Model of Neuropathogenic Escherichia coli Infection in the Neonatal Rat
Published on: October 29, 2014
Effect of the NMDA-receptor antagonist dextromethorphan in infant rat pneumococcal meningitis
Johann Sellner1, Ralph Ringer, Pierre Baumann
1Department of Neurology, Inselspital, Bern University Hospital, Switzerland.
Abstract:
Excitatory amino acids (EAA) and particularly glutamate toxicity have been implicated in the pathogenesis of neuronal injury occurring in bacterial meningitis by activating the N-methyl-d aspartate (NMDA) receptor complex. Here, we evaluated the effect of adjuvant treatment with the antitussive drug dextromethorphan (DM), a non-competitive NMDA receptor antagonist with neuroprotective potential, in an infant rat model of pneumococcal meningitis. The experiments were carried out in postnatal day 6 (P6) and 11 (P11) animals. Pharmacokinetics of DM and its major metabolite dextrorphan (DO) were performed for dose finding. In our study, DM did not alter clinical parameters (clinical score, motor activity, incidence of seizures, spontaneous mortality) and cortical neuronal injury but increased the occurrence of ataxia (P<0.0001). When DM treatment was started at the time of infection (DM i.p. 15 mg/kg at 0, 4, 8 and 16 hours (h) post infection) in P11 animals, an aggravation of apoptotic neuronal death in the hippocampal dentate gyrus was found (P<0.05). When treatment was initiated during acute pneumococcal meningitis (DM i.p. 15 mg/kg at 12 and 15 h and 7.5 mg/kg at 18 and 21 h after infection), DM had no effect on the extent of brain injury but reduced the occurrence of seizures (P<0.03). We conclude that in this infant rat model of pneumococcal meningitis interference of the EEA and NMDA pathway using DM causes ataxia, attenuates epileptic seizures and increases hippocampal apoptosis, but is not effective in protecting the brain from injury.
Insights
Dextromethorphan (DM) did not protect infant rats from brain injury during pneumococcal meningitis, but it did reduce seizures. However, DM treatment increased ataxia and hippocampal apoptosis in this model.
Area of Science:
- Neuroscience
- Pharmacology
- Infectious Diseases
Background:
- Bacterial meningitis can cause neuronal injury via excitatory amino acid (EAA) and N-methyl-D-aspartate (NMDA) receptor activation.
- Dextromethorphan (DM), an NMDA receptor antagonist, has shown neuroprotective potential.
Purpose of the Study:
- To evaluate the efficacy of dextromethorphan (DM) as an adjuvant therapy in an infant rat model of pneumococcal meningitis.
- To assess the impact of DM on neuronal injury, clinical parameters, and specific neurological deficits.
Main Methods:
- Infant rats (postnatal days 6 and 11) were infected with Streptococcus pneumoniae.
- Pharmacokinetics of DM and its metabolite dextrorphan (DO) were determined for dose selection.
- DM was administered at different time points (prophylactic and therapeutic) relative to infection.
- Clinical parameters, motor activity, seizures, mortality, and cortical/hippocampal neuronal injury were assessed.
Main Results:
- DM treatment did not alter clinical scores, motor activity, or overall cortical neuronal injury.
- DM administration increased the incidence of ataxia (P<0.0001) and aggravated apoptotic neuronal death in the hippocampus when given prophylactically.
- Therapeutic DM administration reduced the occurrence of seizures (P<0.03) but did not protect against brain injury.
Conclusions:
- Dextromethorphan (DM) does not protect against brain injury in this infant rat model of pneumococcal meningitis.
- DM interferes with the excitatory amino acid (EAA) and NMDA pathway, leading to ataxia and increased hippocampal apoptosis.
- While DM attenuates seizures, its overall therapeutic benefit in bacterial meningitis is limited in this model.
