Anomalously High Concentrations of Brain Extracellular Uric Acid Detected with Chronically Implanted Probes: Implications for In Vivo Sampling Techniques

Abstract

The height of peak 2, h2, recorded using linear sweep voltammetry with 350-micron-diameter carbon paste electrodes in rat striatum was measured from the day of implantation (day 0) to 4 months after surgery. The value of h2 was at a minimum on day 0 (0.6 +/- 0.2 nA; n = 20), rose sharply to a maximum on day 2 (6.3 +/- 0.9 nA; n = 12), and decreased to a stable level by day 7 (3.3 +/- 0.7 nA; n = 16), which lasted for 4 months (3.2 +/- 0.6 nA; n = 9). These changes were shown by microinfusion of uricase to be due to variations in the concentrations of extracellular uric acid, although h2 appears to have a small baseline contribution of approximately 0.3 nA from 5-hydroxyindoleacetic acid. The stable value of h2 recorded under chronic conditions was estimated to correspond to a minimal uric acid concentration of 50 mumol/L, which represents a 10-fold increase in the extracellular level of this purine metabolite compared with the initial (acute) value. Very similar results were obtained using a microdialysis technique that detected uric acid directly. These estimates of striatal uric acid concentration are in marked contrast to those obtained using 40-micron diameter carbon fiber electrodes, which showed a decrease from the acute preparation to less than 1 mumol/L under chronic conditions. Large values of h2 were also recorded with chronically implanted paste electrodes in the hippocampus and frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)