Effects of Chronic Topiramate, Lacosamide, and Levetiracetam Pre-treatment on a Status Epilepticus Model in Rat Pups

We examined possible neuroprotective and prophylactic effects of chronic pre-treatment with levetiracetam (Lev), topiramate (Tpm), and lacosamide (Lcm) on the pentylenetetrazol (PTZ)-induced status epilepticus (SE) in rat pups. Forty-six rats were divided into four groups; all of them were on postnatal day (PD) 21 i.p. injected with 60 mg/kg PTZ. Rat pups of three experimental groups were pre-treated during 14 days (PD7–PD21) with Tpm, Lcm, or Lev via gavage in doses of 60, 50, and 150 mg/kg per day, respectively; animals of the PTZ group were treated with 0.2 ml saline per day. Animals of the latter group demonstrated intense behavioral changes of a stage 3 of the Racine scale or higher, while no significant behavioral alterations were observed in all pre-treated groups. Protein carbonyl and TBARS levels were markedly elevated in the PTZ group, while these indices were significantly smaller in the Tpm and Lev groups. Immunohistochemical analysis demonstrated an increased apoptosis level in hippocampal pyramidal neurons in the Lev group with respect to the PTZ group. In the open field test, the total distance moved and duration of stay in the outer squares were significantly greater in the PTZ group than in the Lcm and Lev groups. Thus, Tpm, Lcm, and Lev treatment provided clear prophylactic effects on the PTZ-induced SE development; such treatment decreased the intensity of oxidative stress and protected from changes in locomotor activity and anxietyrelated behavior in immature organisms. However, some pro-apoptotic action of Lev on the developing hippocampus needs to be noted and investigated in more detail.