Effect of probenecid on cerebral and cisternal cerebrospinal fluid lactate content.

In this study, the cisternal CSF contents of lactate and glucose were sequentially measured in free-moving rats that had been administered probenecid, 200 mg/kg-1, drug diluent, or no injections. In animals receiving either no injections or injections of drug diluent, CSF lactate and glucose were constant over a 6-h period (93-106% of control), whereas rats receiving probenecid showed increased lactate at 1 and 2 h (170 and 125% control, respectively) and increased glucose at 1, 2, and 3 h (169, 141 and 129% control, respectively). Cerebral cortex content of energy metabolites and lactate and blood lactate levels were statistically unaltered at 0.5-6 h exposure to probenecid, whereas cerebral and blood glucose contents were increased after 1 and 2 h exposure to probenecid. Rats exposed to 5% O2 and probenecid for 0.5 h showed a statistically higher CSF lactate at 0.5 and 1.5 h reoxygenation (169 and 168% control, respectively). A similar effect was also seen in rats exposed to 5% O2 and the 5-hydroxyindoleacetic acid (5-HIAA) transport inhibitor Na divalproate. The results suggested that the increase in CSF glucose was secondary to a probenecid-induced elevation of blood glucose, whereas the increase in CSF lactate seemed to be secondary to a reduced rate of efflux of lactate from the CSF. It is suggested that it may be possible to increase the CSF lactate content by mechanisms that are independent of direct effects on the processes of cerebral energy metabolism.