Levetiracetam protects against kainic acid-induced toxicity

Abstract

We investigated the Levetiracetam (LVT) ability to protect the brain against kainic acid (KA) induced neurotoxicity. Brain injury was induced by intraperitoneal administration of KA (10 mg/kg). Sham brain injury rats were used as controls. Animals were randomized to receive either LVT (50 mg/kg) or its vehicle (1 ml/kg) 30 min. before KA administration. Animals were sacrificed 6 hours after KA injection to measure brain malonildialdehyde (MDA), glutathione levels (GSH) and the mRNA for interleukin-1β (IL-1β) in the cortex and in the diencephalon. Behavioral changes were also monitored. Intraperitoneal administration of LVT decreased significantly MDA in the cortex (KA + vehicle = 0.25 ± 0.03 nmol/mg protein; KA + LVT = 0.13 ± 0.01 nmol/mg protein; P < 0.005), and in the diencephalons (KA + vehicle = 1,01 ± 0.2 nmol/mg protein; KA + LVT = 0,33 ± 0,08 nmol/mg protein; P < 0.005), prevented the brain loss of GSH in both cortex (KA + vehicle = 5 ± 1 μmol/g protein; KA + LVT = 15 ± 2 μmol/g protein; P < 0.005) and diencephalons (KA + vehicle = 9 ± 0.8 μmol/g protein; KA + LVT = 13 ± 0.3 μmol/g protein; P < 0.05), reduced brain IL-1β mRNA and markedly controlled seizures. Histological analysis showed a reduction of cell damage in LVT treated samples. The present data indicate that LVT displays neuro-protective effects against KA induced brain toxicity and suggest that these effects are mediated, at least in part, by inhibition of lipid peroxidation.