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BACKGROUND Epilepsy is a complex neurologic disorder with abnormal electrical impulses in the brain. A crucial role of purinergic signalling in the proper working of the nervous system has been reported but much less is known about the modulation of P2X3 purinergic receptors in epilepsy. This study investigated the effect of NF110, a potent P2X3 receptor antagonist, in the rat epilepsy model of pentylenetetrazole (PTZ)-induced kindling. MATERIAL AND METHODS The mean kindling score, motor activity, locomotion, emotional tension, anxiety, discrimination ability, learning, memory, serum neuron-specific enolase (sNSE), hippocampal IL-1β and TNF-α, thiobarbituric acid-reactive substance (TBARS), catalase (CAT) and reduced glutathione (GSH), and mitochondrial complex I, II, and IV levels of PTZ-kindling animals were assessed. RESULTS The PTZ-kindling animals have shown impaired motor activity, locomotion, discrimination ability, learning, and memory, along with increased emotional tension, anxiety, neuronal damage (increased sNSE), hippocampal pro-inflammatory mediators (increased IL-1β and TNF-α), oxidative stress (increased TBARS, decreased GSH and CAT), and mitochondrial dysfunction. The administration of NF110 in 3 different doses has significantly and dose-dependently corrected PTZ-kindling-induced impaired behavior, learning, memory, locomotion, motor activity, discrimination ability, neuronal damage, hippocampal inflammation, oxidative stress, and mitochondrial dysfunction. These beneficial effects of NF110 in PTZ-kindling animals were significantly abolished by the administration of the P2X agonist α, β methylene-ATP. CONCLUSIONS P2X3 receptors play a very important role in kindling epilepsy and further research should be done to design P2X3 modulators for their possible therapeutic benefits in epileptic disorders.

This work aims to explore the efficacy of Rho kinase inhibitor Fasudil on cognitive impairment induced by chronic cerebral hypoperfusion in rats. A total of 32 male adult Sprague Dawley (SD) rats were randomly divided into three groups: treatment group, control group and sham-operated group for severe carotid artery stenosis model. After two weeks, 8.35 mg/kg Fasudil and physiological saline were intraperitoneally applied twice per day in treatment group and control group, respectively. Morris water maze test was performed in each group to detect the changes of cognitive function and observe the hippocampal pathomorphology in rats after eight weeks. The average escape latency distinctly shortened (P 0.05). Fasudil effectively improved hippocampal pathomorphology. Rho kinase inhibitor obviously ameliorated cognitive impairment induced by chronic cerebral hypoperfusion in rats.

Epilepsy is a common and devastating neurological disorder. Inflammatory processes and apoptosis in brain tissue have been reported in human epilepsy. Scoparone (6,7-dimethoxycoumarin) is an important chemical substance, which has multiple beneficial activities, including antitumor, anti-inflammatory and anti-coagulant properties. In our present study, we attempted to investigate if scoparone could attenuate seizures-induced blood brain barrier breakdown, inflammation and apoptosis. Pilocarpine (Pilo) and methylscopolamine were used to establish acute seizure animal model. Scoparone suppressed the leakage of blood brain barrier, inflammation and apoptosis. In hippocampus and cortex, the expression of inflammation-associated molecules, such as chemokine (CXC motif) ligand 1 (CXCL-1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, hypoxia-inducible factor 1α (HIF-1α), and monocyte chemoattractant protein-1 (MCP-1), were reduced by scoparone through inactivating toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) pathway. Scoparone reduced apoptotic levels in hippocampus by TUNEL analysis, along with decreased Caspase-3 and PARP cleavage. In addition, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway in Pilo-induced acute seizures was also inactivated by scoparone. In vitro, we confirmed that scoparone inhibited LPS-caused astrocytes activation as proved by the reduced glial fibrillary acidic protein (GFAP) levels, inflammation and apoptosis, which were at least partly dependent on AKT suppression. The results above indicated that scoparone could relieve pilocarpine (Pilo)-induced seizures against neural cell inflammation and apoptosis.