LPS-induced oxidative stress and inflammatory reaction in the rat striatum.

BACKGROUND Inflammation-induced microglia activation and increased oxidative stress have been observed in neurodegenerative disorders, such as Parkinson's disease. The aim of our study was to determine the appropriate dose and route of LPS administration to study hydroxyl radical generation and extracellular level of dopamine (DA), glutamate (GLU) and adenosine (ADN) in the rat striatum as markers of DA neuron damage and glial cell activation. The effect of LPS administration on DA, DOPAC, HVA and hydroxyl radical tissue level was also examined. METHODS LPS was given to rats in a single dose of 10 mg/kg ip, repeatedly for 5 days in a dose of 5 mg/kg ip and intrastriatally at doses 5, 20 and 40 μg/4 μl. The extracellular level of DA, hydroxyl radical, ADN and GLU were assayed in striatal dialysates using HPLC with electrochemical, fluorescence and VIS detection, respectively. RESULTS A single ip LPS (10 mg/kg) administration increased hydroxyl radical production but did not affect extracellular DA, GLU and ADN level. Repeated ip LPS (5 × 5 mg/kg) treatment decreased extracellular level of DA, GLU, ADN and production of hydroxyl radical. LPS (5 and 10 μg) given intrastriatally increased hydroxyl radical production, extracellular GLU and ADN level from 0 to 180 min after administration, but did not influence DA level. LPS (5, 20 and 40 μg) decreased striatal DA and DOPAC content, but increased HVA and hydroxyl radical level 72 h after intrastriatal administration. CONCLUSIONS Our data indicate that local intrastriatal LPS administration activates glial cells and increases production of free radicals and secretion of GLU and ADN in early phase of inflammation. The damage of DA neurons is observed 72 h after local LPS administration.