Protective effects of the ROCK inhibitor fasudil against cognitive dysfunction following status epilepticus in male rats

Rho/ROCK signaling activated following status epilepticus (SE) may be involved in the pathological process of hippocampus damages, epileptogenesis, and cognitive deficits. AbstractDespite remarkable advances in epilepsy research, prevention and reversal of cognitive deficits following epilepsy remain a challenge. It was reported that the Rho kinase (ROCK) inhibitor fasudil hydrochloride (FH) could improve cognitive deficits in animal models of Alzheimer ’s disease (AD). Thus, the aim of the present study was to determine whether FH–mediated inhibition of the effects of ROCK signaling could improve cognitive deficits in male rats (postnatal 21‐day old) following status epilepticus (SE) induced by lithium‐pilocarpin, the therapeutic window of opportunity and to elucidate the underlying mechanisms. Western blotting analysis showed upregulation of phosphorylated RhoA (p‐RhoA) expression, and indicated activation of Rho/ROCK signaling after SE. The Morris water maze (MWM) test was used to analyze learning‐memory ability. HE staining, i mmunofluorescence staining with antineuronal nuclei (NeuN) and anti‐neurofilament proteins 200 kD (NF200), transmission electron microscopy, and quantitative analysis of NeuN and synaptophysin by western blotting were performed to observe alterations in neurons, axons, and synapses in the hippocam pi. Electroencephalogram (EEG) monitoring was used to record electrophysiological activities after SE. Our results indicated that treatment ...
Source: Journal of Neuroscience Research - Category: Neuroscience Authors: Tags: RESEARCH ARTICLE Source Type: research