Infant Rat Model Of Meningitis Research Articles

Blockade of NMDA receptor subtype NR2B prevents seizures but not apoptosis of dentate gyrus neurons in bacterial meningitis in infant rats

BackgroundExcitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis. The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol (RO 25-6981). Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae. Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28) or 3.75 mg (150 mg/kg; n = 15) every 3 h or an equal volume of sterile saline (250 μl; n = 40) starting at 12 h after infection. Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h. At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus.ResultsTreatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P < 0.05 for all RO 25-6981 treated animals combined). The extent of apoptosis was not affected by low or high doses of RO 25-6981. Number of apoptotic cells (median [range]) was 12.76 [3.16–25.3] in animals treated with low dose RO 25-6981 (control animals 13.8 [2.60–31.8]; (P = NS) and 9.8 [1.7–27.3] (controls: 10.5 [2.4–21.75]) in animals treated with high dose RO 25-6981 (P = NS).ConclusionsTreatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures.

Interactions of Haemophilus influenzae with human endothelial cells in vitro.

Journal Article Interactions of Haemophilus influenzae with Human Endothelial Cells In Vitro Get access Mumtaz Virji, Mumtaz Virji Molecular Infectious Diseases Group, Department of Paediatrics, and Nuffield Department of Pathology, John Radcliffe Hospital, Search for other works by this author on: Oxford Academic PubMed Google Scholar Helena Käyhty, Helena Käyhty Molecular Infectious Diseases Group, Department of Paediatrics, and Nuffield Department of Pathology, John Radcliffe Hospital, Search for other works by this author on: Oxford Academic PubMed Google Scholar David J. P. Ferguson, David J. P. Ferguson Molecular Infectious Diseases Group, Department of Paediatrics, and Nuffield Department of Pathology, John Radcliffe Hospital, Search for other works by this author on: Oxford Academic PubMed Google Scholar Carol Alexandrescu, Carol Alexandrescu Molecular Infectious Diseases Group, Department of Paediatrics, and Nuffield Department of Pathology, John Radcliffe Hospital, Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Richard Moxon E. Richard Moxon Molecular Infectious Diseases Group, Department of Paediatrics, and Nuffield Department of Pathology, John Radcliffe Hospital, Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 165, Issue Supplement_1, June 1992, Pages S115–S116, https://doi.org/10.1093/infdis/165-Supplement_1-S115 Published: 01 June 1992