Subchronic cerebrolysin treatment alleviates cognitive impairments and dendritic arborization alterations of granular neurons in the hippocampal dentate gyrus of rats with temporal lobe epilepsy

Abstract

Temporal lobe epilepsy (TLE) is one of the most frequent forms of focal epilepsy; patients with this condition, in addition to exhibiting complex seizures, also exhibit cognitive deficits. In the temporal lobe, the hippocampus, a structure relevant to learning and memory processes, is particularly affected by epilepsy. In animal models of TLE induced by pilocarpine, learning and memory deficiencies associated with changes in synaptic plasticity of the hippocampus have been reported. Cerebrolysin (CBL) is a biologically active mixture of low molecular weight peptides with neuroprotective and neurotrophic effects. The objective of the present study was to determine whether subchronic CBL treatment of rats in the chronic phase of TLE reduces the number and intensity of seizures, and whether CBL treatment can improve cognitive deficits (learning and spatial memory) and dendritic morphology in granular dentate neurons of the hippocampus. Temporal lobe epilepsy (lithium-pilocarpine model) was induced in male Wistar rats (weight, 250-300 g). Two epileptic groups were studied, in which CBL (538 mg/kg) or vehicle was administered intraperitoneally for 5 consecutive days per week for 3 weeks. Respective controls were also included in the study. At the end of treatment, the Barnes maze test (BMT) was used to assess spatial navigational learning and memory. The dendritic morphology of the dentate gyrus was also evaluated using the Golgi-Cox staining method. Results of this study did not support an antiepileptic effect of CBL. Epileptic animals treated with this agent exhibited secondarily generalized seizures similar in frequency and intensity to those of epileptic animals treated only with vehicle. However, when analyzing dendritic morphology of hippocampal granular neurons in these animals, CBL appeared to attenuate dendritic deterioration caused by epilepsy, which was associated with improved cognitive performance of the CBL-treated animals in the BMT compared with vehicle-treated epileptic rats. In conclusion, although CBL did not exert an anticonvulsant effect against secondarily generalized seizures, it can be proposed for use as an add-on therapy in epilepsy management to prevent neuronal alterations, and to improve memory and learning processes.

Keywords: Barnes maze test; Cerebrolysin; Dendritic morphology; Temporal lobe epilepsy.