Effect of Rufinamide on the kainic acid-induced excitotoxic neuronal death in the mouse hippocampus.

Rufinamide (RUF) is a structurally unique anti-epileptic drug, used in the treatment of seizure disorders such as Lennox-Gastaut syndrome. In the present study, we investigated whether RUF protected against excitotoxic neuronal damage in the mouse hippocampal CA3 region after intraperitoneal kainic acid (KA) injection. Treatment with 25, 50 and 100 mg/kg RUF significantly decreased the KA-induced neuronal death in the hippocampal CA3 region in a dose-dependent manner. In addition, 100 mg/kg RUF treatment reduced the KA-induced oxidative stress-related increase of MDA level and decrease of total SOD activity in the hippocampus. KA-induced increases of pro-inflammatory cytokines, TNF-α and IL-1ß, levels as well as KA-induced microglial activation were also suppressed by RUF treatment. These results indicate that RUF displays a neuroprotective effect against KA-induced excitotoxic neuronal death in the mouse hippocampus through anti-oxidant and anti-inflammatory activities.

The anti-inflammatory activity of duloxetine, a serotonin/norepinephrine reuptake inhibitor, prevents kainic acid-induced hippocampal neuronal death in mice.

Duloxetine (DXT), a potent serotonin/norepinephrine reuptake inhibitor, is widely used in the treatment of major depressive disorder. In the present study, we examined the effects of DXT treatment on seizure behavior and excitotoxic neuronal damage in the mouse hippocampal CA3 region following intraperitoneal kainic acid (KA) injection. DXT treatment showed no effect on KA-induced behavioral seizure activity. However, treatment with 10mg/kg DXT reduced KA-induced neuronal death in the hippocampal CA3 region at 72h after KA administration, and treatment with 20 and 40mg/kg DXT showed a noticeable neuroprotection in the hippocampal CA3 region after KA injection. In addition, KA-induced activations of microglia and astrocytes as well as KA-induced increases of TNF-α and IL-1ß levels were also suppressed by DXT treatment. These results indicate that DXT displays the neuroprotective effect against KA-induced excitotoxic neuronal death through anti-inflammatory action.