Epileptogenesis

About: Epileptogenesis is a research topic. Over the lifetime, 4218 publications have been published within this topic receiving 170809 citations.

The roles of metabotropic glutamate receptors in seizures and epilepsy.

Abstract: Epilepsy is a disorder that afflicts more than 50 million people worldwide. Current antiepileptic drugs (AEDs), although effective in controlling seizures for the majority of individuals, remain far from ideal as therapeutics. There is a need for new drugs that act at different molecular targets than currently available AEDs and for new therapies designed to block the process of epileptogenesis. Because of their central role in modulating numerous physiological processes in the central nervous system, metabotropic glutamate receptors (mGluRs) have been implicated in the pathophysiology of a variety of neurological conditions including epilepsy. mGluRs represent attractive new targets for therapeutic control of seizures and interruption of the epileptogenic process. We review the involvement of mGluRs in the induction and expression of epileptic seizures, their potential roles in the process of epileptogenesis, and their altered expression and function in the epileptic human brain.

Anti-inflammatory drugs in epilepsy: does it impact epileptogenesis?

Abstract: Introduction: In the epilepsy therapeutic arena, there is urgent need for developing novel antiepileptogenesis treatments that offer a way to prevent the onset or the progression of the disease. Such treatments are still lacking, and their development requires a deep understanding of the mechanisms underlying the disease pathogenesis, in order to target them using appropriate drugs with timely interventions.Areas covered: Preclinical research highlighted glial cells in seizure-prone areas as key contributors to neuronal circuit hyperexcitability resulting in seizures. Microglia and astrocytes activated by epileptogenic insults increase their synthesis and release of pro-inflammatory molecules, thus contributing to the generation of neuroinflammation. This is now considered an established hallmark of epileptogenic foci in various forms of pharmaco-resistant epilepsies. Studies done in experimental models of non-genetic forms of epilepsy demonstrated that specific inflammatory molecules are involved in seiz...

Neurocysticercosis: A natural human model of epileptogenesis.

Abstract: Objective To develop a better understanding on mechanisms of seizures and long-term epileptogenesis caused by neurocysticercosis.

Developmental impact of a familial GABAA receptor epilepsy mutation.

Abstract: Epilepsy, with a lifetime prevalence rate of 3%, is a common and serious neurological disorder. It is characterized by recurrent paroxysms resulting from hypersynchronous discharges in the brain. Mutations in more than a dozen ion channel genes have been associated with familial epilepsy syndromes providing a strong foundation on which to build an understanding of epileptogenesis. Ion channels have an acute role setting the real-time excitability of neurons and networks, and a developmental role in the coupling of neurons in networks. When mutations occur, they may influence either role to varying degrees to cause the clinical phenotype. Distinguishing acute from developmental roles has important therapeutic implications. Reversing the consequences of developmental dysfunction may not be a simple matter of compensating for the acute receptor deficit because the developmental consequences may be inherent in neural networks of patients with epilepsy. There is no evidence that familial disease causing ion channel mutations impacts neural development. Mouse models harboring human epilepsy-causing mutations that recapitulate aspects of the human disease are particularly valuable models to test the link between gene mutation and seizures. Manipulation of the temporal expression of a single mutation may provide a means to resolving the impact of a mutation on the developing and adult brain. To this end, we engineered a mouse model in which we can manipulate the temporal expression of a GABAA γ2 mutation, previously reported in a large Australian family with febrile seizures and generalized epilepsy.1 GABAA receptors are ligand-gated chloride channels and arbiters of fast inhibitory neurotransmission in the adult brain. Perturbation of fast inhibition has been linked to seizure genesis. During brain development, GABAA receptors also play an important role in regulating neuronal differentiation, proliferation, and synaptogenesis2 that can also influence seizure genesis. Here, we generate and characterize a conditional mouse model that allows a forebrain-specific switch of a human epilepsy GABAA γ2 (R43Q) mutation at specific times during development. Using this mouse, we demonstrate that expression of GABAA γ2 (R43Q) in the developing brain increases seizure susceptibility in adulthood.