Effects of Topiramate on the Brain Cell Energy Metabolism in the Early Phase of Experimental Escherichia coli Meningitis

ABSTRACT

PURPOSE: Topiramate is a novel antiepileptic drug, and is known to act as a glutamate receptor antagonist. Excitotoxicity by glutamate is also advocated as an arm of brain injury in bacterial meningitis. We sought to delineate whether topiramate could attenuate brain energy depletion during bacterial meningitis by near infrared spectroscopy monitoring. METHODS: Meningitis was induced by intracisternal injection of 108 colony forming units of Escherichia coli. Topiramate at a dose of 50 or 100 mg/kg was given to the piglets 30 minutes before the induction of meningitis. The piglets in the meningitis control group were not given topiramate. Cerebral blood volume, cerebral blood flow, and brain cell energy state were monitored for 6 hours by near infrared spectroscopy. RESULTS: 100 mg/kg of topiramate significantly attenuated the increase in intracranial pressure and leukocyte count in the cerebrospinal fluid during study period. Although statistically insignificant, there was a trend of decrease in cerebral blood volume as indicated by total hemoglobin and cerebral blood flow as indicated by oxidized hemoglobin. Deduced hemoglobin in the meningitis was attenuated by topiramate. Topiramate did not significantly affect the brain energy state as indicated by cytochrome aa3 during the 6 hours after the induction of meningitis. CONCLUSION: 100 mg/kg of topiramate significantly attenuated the inflammatory response in experimentally induced bacterial meningitis. However, there was no significant effect of topiramate on the brain cell energy metabolism during the early phase of experimental bacterial meningitis.