Marked elevation in cortical urate and xanthine oxidoreductase activity inexperimental bacterial meningitis

Experimental bacterial meningitis due to Streptococcus pneumoniae in infant rats was associated with a time-dependent increase in CSF and cortical ura te that was similar to 30-fold elevated at 22 h after infection compared to baseline. This increase was mirrored by a 20-fold rise in cortical xanthin e oxidoreductase activity. The relative proportion of the oxidant-producing xanthine oxidase to total activity did not increase, however. Blood plasma levels of urate also increased during infection, but part of this was as a consequence of dehydration, as reflected by elevated ascorbate concentrati ons in the plasma. Administration of the radical scavenger alpha -phenyl-te rt-butyl nitrone, previously shown to be neuroprotective in the present mod el, did not significantly affect either xanthine dehydrogenase or xanthine oxidase activity, and increased even further cortical accumulation of urate . Treatment with the xanthine oxidoreductase inhibitor allopurinol inhibite d CSF urate levels earlier than those in blued plasma, supporting the notio n that urate was produced within the brain. However, this treatment did not prevent the loss of ascorbate and reduced glutathione in the cortex and CS F. Together with data from the literature. the results strongly suggest tha t xanthine oxidase is nor a major cause of oxidative stress in bacterial me ningitis and that urate formation due to induction of xanthine oxidoreducta se in the brain may in fact represent a protective response. (C) 2001 Elsev ier Science B.V. All rights reserved.