Dehydroepiandrosterone Attenuates Astroglial Activation, Neuronal Loss and Dendritic Degeneration in Iron-Induced Post-Traumatic Epilepsy

Abstract

Iron-induced experimental epilepsy in rodents reproduces features of post-traumatic epilepsy (PTE) in humans. The neural network of the brain seems to be highly affected during the course of epileptogenesis and determines the occurrence of sudden and recurrent seizures. The aim of the current study was to evaluate astroglial and neuronal response as well as dendritic arborization, and the spine density of pyramidal neurons in the cortex and hippocampus of epileptic rats. We also evaluated the effect of exogenous administration of a neuroactive steroid, dehydroepiandrosterone (DHEA), in epileptic rats. To induce epilepsy, male Wistar rats were given an intracortical injection of 100 mM solution (5 µL) of iron chloride (FeCl3). After 20 days, DHEA was administered intraperitoneally for 21 consecutive days. Results showed epileptic seizures and hippocampal Mossy Fibers (MFs) sprouting in epileptic rats, while DHEA treatment significantly reduced the MFs’ sprouting. Astroglial activation and neuronal loss were subdued in rats that received DHEA compared to epileptic rats. Dendritic arborization and spine density of pyramidal neurons was diminished in epileptic rats, while DHEA treatment partially restored their normal morphology in the cortex and hippocampus regions of the brain. Overall, these findings suggest that DHEA’s antiepileptic effects may contribute to alleviating astroglial activation and neuronal loss along with enhancing dendritic arborization and spine density in PTE.