Chronic treatment with levetiracetam reverses deficits in hippocampal LTP in vivo in experimental temporal lobe epilepsy rats

Abstract Temporal lobe epilepsy (TLE), the common form of epilepsy in adults, often displays complex partial seizures and cognitive deficits. The underlying mechanisms of such deficits are not yet well understood. Many contributing factors, such as initial epileptogenic lesion, seizure type, age of onset, and treatment side effects have been proposed. Levetiracetam (LEV) is a novel anti-epileptic drug (AED) used to treat partial seizures and idiopathic generalized epilepsy. It has been suggested that LEV exerts antiepileptic properties by modulation of synaptic release of neurotransmitters. However, its neuroprotective effects on learning and memory are not yet well demonstrated. Here we showed the impairment of spatial memory in the pilocarpine-induced experimental TLE rats, which can be improved by LEV. Furthermore, we found chronic LEV treatment partially reversed the SE-induced synaptic dysfunction in hippocampal LTP induction in vivo . In addition, LEV treatment can alleviate the SE-induced abnormal GluR1 phosphorylation at Ser 831 site, which may contribute to the rescue of synaptic transmission. These results indicate the neuroprotective role for LEV while it exhibits an antiseizure effect on experimental epileptic models.