Dataset Information

Antiepileptic effects of exogenous ?-hydroxybutyrate on kainic acid-induced epilepsy.

ABSTRACT: The aim of the present study was to explore the potential anticonvulsant effects of ?-hydroxybutyrate (BHB) in a kainic acid (KA)-induced rat epilepsy model. The KA-induced rat seizure model was established and BHB was administrated intraperitoneally at a dose of 4 mmol/kg 30 min prior to KA injection. Hippocampal tissues were then obtained 1, 3 and 7 days following KA administration, following which the expression levels of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) were measured using a double immunofluorescence labeling method. In addition, the contents of glutathione (GSH), ?-aminobutyric acid (GABA) and ATP were measured using ELISA. Pretreatment with BHB markedly increased the expression of NSE after KA injection compared with that in the normal saline (NS) + KA group, suggesting that the application of BHB could alleviate neuronal damage in rats. The protective effect of BHB may be associated with suppressed inflammatory responses, which was indicated by the observed inhibition of GFAP expression in rats in the BHB + KA group compared with that in the NS + KA group. It was also found that GSH and GABA contents were notably increased after the rats were pretreated with BHB compared with those in the NS + KA group. To conclude, the application of exogenous BHB can serve as a novel therapeutic agent for epilepsy.

SUBMITTER: Si J

PROVIDER: S-EPMC7579833 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Antiepileptic effects of exogenous β-hydroxybutyrate on kainic acid-induced epilepsy.

Si Jianping J Wang Yingyan Y Xu Jing J Wang Jiwen J

Experimental and therapeutic medicine 20201009 6

The aim of the present study was to explore the potential anticonvulsant effects of β-hydroxybutyrate (BHB) in a kainic acid (KA)-induced rat epilepsy model. The KA-induced rat seizure model was established and BHB was administrated intraperitoneally at a dose of 4 mmol/kg 30 min prior to KA injection. Hippocampal tissues were then obtained 1, 3 and 7 days following KA administration, following which the expression levels of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP ...[more]

PMID: 33101467

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Project description:Mesial Temporal Lobe Epilepsy (MTLE) is a chronic disease characterized by recurrent unprovoked partial seizures. Current treatments lack long-term efficacy and typically act only to ameliorate the symptomology, rather than to modify the course of the disease. Chronic kainic acid (KA)-induced models of MTLE mimic prominent histopathological and electroencephalographic features of human MTLE, including hippocampal sclerosis, CA1 neuronal loss, astrogliosis, microgliosis, and electrographic hippocampal discharges. Here we examined the transcriptional profiles of the hippocampus of KA - vs sham-injected mice from epileptogenesis to the stabilization of spontaneous recurring seizures. KA (1 nmol) or saline (sham) was injected unilaterally into the dorsal hippocampus of 12 week old C57BL/6J mice, and the ipsilateral (IL) and contralateral (CL) hippocampi were isolated for whole-genome expression profiling (Illumina microarray) or immunohistochemistry 7, 28 and 60 d later. Differential gene expression analysis of the IL hippocampus indicated that 1349, 484, and 439 genes were significantly (fdr<0.05) altered in KA compared to sham at 7, 28 and 60 d, respectively. 108 genes were altered at all time-points assessed, while others were altered in a time-dependent manner, indicative of distinct hippocampal gene expression profiles across the course of disease. Ingenuity Pathway Analysis revealed that specific immune cell and inflammatory signaling pathways were upregulated at 7 and 28 d, in support of a role of neuroinflammation in the disease etiology. The top canonical pathways profile at 60 d was quite distinct from that at 7 and 28 d, although certain inflammatory pathways were still prevalent, indicative of pathways involved in the maintenance of the disease. Consistent with a role of neuroinflammation in MTLE, immunohistochemical analyses demonstrated time-dependent changes in both the intensity of immunoreactivity and number of Iba1- and GFAP-positive cells. To reveal gene networks not apparent with differential expression data alone, weighted gene co-expression analysis (WGCNA) was performed. A gene network that highly associated with 7 d IL-KA (but not 28 and 60 d) was identified, which may point to changes involved in the process of epileptogenesis. Another gene network revealed a group of genes highly associated with changes occurring at 28 and 60 d, but not 7 d, which may point to molecules involved in the generation of spontaneous recurring seizures. Collectively, results indicate that specific pathways, including many associated with neuroinflammation, are activated in a time-dependent manner in MTLE.

Dataset Information

Antiepileptic effects of exogenous ?-hydroxybutyrate on kainic acid-induced epilepsy.

Publications

Antiepileptic effects of exogenous β-hydroxybutyrate on kainic acid-induced epilepsy.

Similar Datasets

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