Abstract
Purpose: To investigate the function and potential therapeutic relevance of butyrate in epilepsy using rat models of kainic acid (KA)-induced epilepsy.Methods: The neurotoxin KA was applied to rats and rat astrocytes to establish models of epilepsy in vivo and in vitro. Multiple parameters, including behavioural seizure scores, were evaluated in rats and rat astrocytes treated with KA alone or in combination with butyrate. Western blot was performed to examine the levels of phosphorylated extracellular signal-related kinase (p-ERK), proinflammatory cytokine (IL-1ß), and glial fibrillary acidic protein (GFAP).Results: Significant increases were observed in the seizure-related proteins p-ERK and GFAP and in the proinflammatory cytokine IL-1ß in KA-treated rats and rat astrocytes (p < 0.05). Butyrate treatment attenuated KA-induced epileptic behaviour in rats and significantly reduced the expression of p-ERK, GFAP, and IL-1ß in a dose-dependent manner (p < 0.05).Conclusion: Butyrate has potential as a treatment for epilepsy by inhibiting the activation of p-ERK, astrogliosis, and inflammation, which were induced by KA in rats and rat astrocytes.Keywords: Kainic acid, Epilepsy, Butyrate, Glial activation, Astrogliosis
Highlights
Epilepsy is a neurological disorder that is accompanied by recurrent seizures due to abnormal hypersynchrony of neuronal activity [1]
To explore a potential therapeutic approach for epilepsy/seizures, this study aimed to investigate the function of butyrate in kainic acid (KA)-induced epilepsy in male adult rats in vivo and rat astrocyte cells in vitro
The findings demonstrate that butyrate has potential as an agent for the treatment of kainic acid (KA)-induced seizures in animals and cultured cells
Summary
Epilepsy is a neurological disorder that is accompanied by recurrent seizures due to abnormal hypersynchrony of neuronal activity [1]. Approximately 30% of patients with epilepsy fail to respond to currently available anti-epileptic drugs [3]. Patients with epilepsy have a life expectancy reduction of up to 2–10 years compared with the general population [4]. It is critically important to identify and develop novel approaches with effective antiepileptogenic or disease-modifying effects [5]. Microglia is known to have neurotoxic and neuroprotective effects in central nervous system diseases [6]. Analyses of deceased humans and patients with intractable seizures demonstrated increases in microglial reactivity to a histocompatibility antigen as great as threefold and 11-fold in the conus ammon (CA) and CA1 regions, respectively [7].
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