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Protective effects of the ROCK inhibitor fasudil against cognitive dysfunction following status epilepticus in male rats
Author(s) -
Song Xiaojie,
He Rong,
Han Wei,
Li Tianyi,
Xie Lingling,
Cheng Li,
Chen Hengsheng,
Xie Mingdan,
Jiang Li
Publication year - 2019
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.24355
Subject(s) - morris water navigation task , neun , rhoa , fasudil , status epilepticus , neuroscience , epilepsy , cognitive deficit , synaptophysin , axon , medicine , pharmacology , psychology , rho associated protein kinase , hippocampus , biology , microbiology and biotechnology , cognition , signal transduction , immunohistochemistry , cognitive impairment
Abstract Despite 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, immunofluorescence 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 hippocampi. Electroencephalogram (EEG) monitoring was used to record electrophysiological activities after SE. Our results indicated that treatment with FH at the first day following SE or 5 days later both could ameliorate cognitive dysfunction by reducing neuron, axon, and synapse damage, and mitigating EEG discharges, suggesting various roles for the Rho/ROCK signaling pathway in the pathological processes of brain damages following SE induced by lithium–pilocarpine. The Rho/ROCK signaling pathway is, therefore, a potential therapeutic target for the prevention or reversal of epilepsy induced brain damages.