Lipopolysaccharide enhances glutaric acid-induced seizure susceptibility in rat pups: Behavioral and electroencephalographic approach

Abstract

Glutaric acidemia type I (GA-I) is an inherited metabolic disease characterized by accumulation of glutaric acid (GA) and seizures. Considering that seizures are precipitated by common infections in children with GA-I, we investigated whether lipopolysaccharide (LPS) modifies GA-induced electrographic and neurochemical alterations in 21 days-old rats. The effect of LPS on convulsive behavior and electroencephalographic (EEG) alterations induced by GA (0.13; 0.4; 1.3 μmol/striatum) was determined in freely moving rats. After EEG recordings, we measured the levels of interleukin 1β (IL-1β) in GA-injected striatum. The injection of LPS (2mg/kg; i.p.) 6h before of GA administration, reduced the latency and increased the duration of seizures induced by GA (1.3 μmol/site). In addition, LPS administration increased IL-1β striatal levels, which positively correlated with total time in seizures. The intrastriatal injection of an IL-1β antibody (200 ng/2 μl) prevented the facilitation of GA-induced seizures by LPS. These data suggest that inflammatory processes during critical periods of development may decrease GA-induced seizure threshold.