Topic
Epileptogenesis
About: Epileptogenesis is a research topic. Over the lifetime, 4218 publications have been published within this topic receiving 170809 citations.
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TL;DR: It is concluded that silk-based adenosine delivery exerts potent anti-ictogenic effects, but might also have at least partial anti-epileptogenic effects and hold promise for the treatment of epilepsy.
103 citations
TL;DR: The results have not only characterized the microRNA expression profile in post status epilepticus rat hippocampus but also demonstrated that some rat hippocampal microRNAs were probably associated with rat peripheral blood micro RNAs.
103 citations
TL;DR: This review discusses how maladaptive changes of adenosinergic mechanisms contribute to the expression of seizures (ictogenesis) and the development of epilepsy (epileptogenesis) by focusing on pharmacological and biochemical mechanisms as well as on enzymatic and transport based mechanisms that control the availability ofadenosine.
103 citations
TL;DR: Inhibition is robust in both of these chronic models of epileptogenesis, and immunocytochemical studies show that there is enhanced immunoreactivity for several proteins in GABAergic interneurons of chronic cortical isolations, and suggest that there may be sprouting of GABAergic axons in the area of injury.
103 citations
TL;DR: In this article, the expression of different multidrug transporters during epileptogenesis in the rat was investigated, and it was shown that MRP overexpression was associated with lower PHT levels in the brain, which was reversed through inhibition of MRPs.
Abstract: Summary: Purpose: Overexpression of multidrug transporters may play a role in the development of pharmacoresistance by decreasing extracellular drug levels in the brain. However, it is not known whether overexpression is due to an initial insult or evolves more gradually because of recurrent spontaneous seizures. In the present study, we investigated the expression of different multidrug transporters during epileptogenesis in the rat. In addition, we determined whether these transporters affected phenytoin (PHT) distribution in the brain.
Methods: Expression of multidrug resistance–associated proteins MRP1 and MRP2 and breast cancer–resistance protein (BCRP) was examined after electrically induced status epilepticus (SE) by immunocytochemistry and Western blot analysis. Brain/blood PHT levels were determined by high-performance liquid chromatography (HPLC) analysis in the presence and absence of the MRP inhibitor probenecid.
Results: Shortly after SE, MRP1, MRP2, and BCRP were upregulated in astrocytes within several limbic structures, including hippocampus. In chronic epileptic rats, these proteins were overexpressed in the parahippocampal cortex, specifically in blood vessels and astrocytes surrounding these vessels. Overexpression was related to the occurrence of SE and was present mainly in rats with a high seizure frequency. Brain PHT levels were significantly lower in epileptic rats compared with control rats, but pharmacologic inhibition of MRPs increased the PHT levels.
Conclusions: Overexpression of MRP and BCRP was induced by SE as well as recurrent seizures. Moreover, overexpression was associated with lower PHT levels in the brain, which was reversed through inhibition of MRPs. These data suggest that administration of antiepileptic drugs in combination with specific inhibitors for multidrug transporters may be a promising therapeutic strategy in pharmacoresistant patients.
103 citations