NEUROPROTECTIVE EFFECT OF EXCITATORY AMINO-ACID ANTAGONIST KYNURENIC ACID IN EXPERIMENTAL BACTERIAL-MENINGITIS

Sustained high-level exposure to glutamate, an excitatory amino acid n eurotransmitter, leads to neuronal death, Kynurenic acid attenuates th e toxic effects of glutamate by inhibition of neuronal excitatory amin o acid receptors, including the N-methyl-D-aspartate subtype, To evalu ate the role of glutamate in causing neuronal injury in a rat model of meningitis due to group B streptococci, animals were treated with kyn urenic acid (300 mg/kg subcutaneously once daily) or saline beginning at the time of infection, Histopathologic examination after 24-72 h sh owed 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 neurona l injury (P < .03) in the cortex and the hippocampus than did untreate d controls, These results suggest an important contribution of glutama te to neurotoxicity in this animal model of neonatal meningitis.