Modulation of axonal sprouting along rostro-caudal axis of dorsal hippocampus and no neuronal survival in parahippocampal cortices by long-term post-lesion melatonin administration in lithium-pilocarpine model of temporal lobe epilepsy

Abstract

Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in melatonin treated lithium-pilocarpine epileptic rats during early and chronic phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction, 5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals were killed 60 days post SE induction and the histological features of the rosrto-caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining. Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. The number of counted granular cells by melatonin (20 mg/kg) treatment increased along the rostro-caudal axis of the dorsal hippocampus in comparison to the untreated epileptic group. The density of Timm granules in the inner molecular layer of the dentate gyrus decreased significantly in all melatonin treated groups in comparison to the untreated epileptic animals. The increased density of synapsin I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated epileptic rats showed a profound decrease following melatonin treatment. There was no neuronal protection in the piriform and entorhinal cortices whatever the melatonin treatment. Long-term melatonin administration as a co-adjuvant probably could reduce the post-lesion histological consequences of TLE in a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus.

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

“…In the pilocarpine-induced SE model, animals treated with melatonin just before, during or after SE, exhibited an increased latency to SE, a survival rate of 100% after SE, a decreased number of seizures in the chronic period and hippocampal neuronal preservation [ 520 ]. Moreover, long-term melatonin administration after SE, reduced neuronal loss showing a region-specific pattern of neuronal protection along the rostro-caudal axis of the dorsal hippocampus [ 521 ]. These results confirm an important role for melatonin in the epileptogenic process as well as the control of seizures.…”

Dynamic Changes in Spectral and Spatial Signatures of High Frequency Oscillations in Rat Hippocampi during Epileptogenesis in Acute and Chronic Stages

“…Dynamic changes in spectral power of pHFOs in CA1 and CA3 were the most significant. Previous studies have shown that models of TLE are characterized by extensive neuronal loss, reactive gliosis, mossy fiber sprouting, granule cell dispersion, and synaptic remodeling in CA1 and CA3 (36, 37), which are the vulnerable regions after SE (38). It is assumed that these pathological changes lead to the genesis of new hyperexcitable circuits that generate SRS, characterizing the chronic phase.…”

Ameliorating impacts of ginseng on the apoptosis of spermatogenic cells and sperm quality in temporal lobe epilepsy rat model treated with valproate

“…We used a TLE induction method reported in our previous studies (Kazemi, Shokri, Ganjkhani, Ali, & Iraj, ). Briefly, rats received intraperitoneal (i.p.)…”