Neuroprotective effect of excitatory amino acid antagonist kynurenic acid in experimental bacterial meningitis.
Sustained high-level exposure to glutamate, an excitatory amino acid neurotransmitter, leads to neuronal death. Kynurenic acid attenuates the toxic effects of glutamate by inhibition of neuronal excitatory amino acid receptors, including the N-methyl-D-aspartate subtype. To evaluate the role of glutamate in causing neuronal injury in a rat model of meningitis due to group B streptococci, animals were treated with kynurenic acid (300 mg/kg subcutaneously once daily) or saline beginning at the time of infection. Histopathologic examination after 24-72 h showed two distinct forms of neuronal injury, areas of neuronal necrosis in the cortex and injury of dentate granule cells in the hippocampus. Animals treated with kynurenic acid showed significantly less neuronal injury (P < .03) in the cortex and the hippocampus than did untreated controls. These results suggest an important contribution of glutamate to neurotoxicity in this animal model of neonatal meningitis.
Infectious Diseases Laboratory, San Francisco General Hospital, California, USA.
S L
SL
Leib
Y S
YS
Kim
D M
DM
Ferriero
M G
MG
Täuber
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001925:Brain Damage, Chronic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology; D002555:Cerebrospinal Fluid / Q000382:microbiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D018698:Glutamic Acid / Q000502:physiology; D007736:Kynurenic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D016920:Meningitis, Bacterial / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013290:Streptococcal Infections / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D013292:Streptococcus agalactiae / Q000302:isolation & purification
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D007736:Kynurenic Acid