The role of inflammation in epilepsy

Vezzani, Annamaria; French, Jacqueline A.; Bartfai, Tamás; Baram, Tallie Z.

doi:10.1038/nrneurol.2010.178

Cited by 1,545 publications

(1,452 citation statements)

References 178 publications

(197 reference statements)

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“…The inhibition of IL-1β production by VX-765 would prevent the increased neuronal excitability mediated by the previously described events, thus reducing epileptic activity. Notably, an antiinflammatory steroid drug, such as dexamethasone [33], which is used for medical treatment of pharmacoresistant seizures ("for details see review by Vezzani et al [44]") was also effective in this model for partly reducing epileptic activity. The effect of dexamethasone was transient lapsing after 4 h of treatment.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice

et al. 2011

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Summary: Experimental evidence and clinical observations indicate that brain inflammation is an important factor in epilepsy. In particular, induction of interleukin-converting enzyme (ICE)/caspase-1 and activation of interleukin (IL)-1β/ IL-1 receptor type 1 axis both occur in human epilepsy, and contribute to experimentally induced acute seizures. In this study, the anticonvulsant activity of VX-765 (a selective ICE/ caspase-1 inhibitor) was examined in a mouse model of chronic epilepsy with spontaneous recurrent epileptic activity refractory to some common anticonvulsant drugs. Moreover, the effects of this drug were studied in one acute model of seizures in mice, previously shown to involve activation of ICE/caspase-1. Quantitative analysis of electroencephalogram activity was done in mice exposed to acute seizures or those developing chronic epileptic activity after status epilepticus to assess the anticonvulsant effects of systemic administration of VX-765.Histological and immunohistochemical analysis of brain tissue was carried out at the end of pharmacological experiments in epileptic mice to evaluate neuropathology, glia activation and IL-1β expression, and the effect of treatment. Repeated systemic administration of VX-765 significantly reduced chronic epileptic activity in mice in a dose-dependent fashion (12.5-200 mg/kg). This effect was observed at doses ≥50 mg/ kg, and was reversible with discontinuation of the drug. Maximal drug effect was associated with inhibition of IL-1β synthesis in activated astrocytes. The same dose regimen of VX-765 also reduced acute seizures in mice and delayed their onset time. These results support a new target system for anticonvulsant pharmacological intervention to control epileptic activity that does not respond to some common anticonvulsant drugs.

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Section: Discussionmentioning

confidence: 99%

Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice

et al. 2011

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“…Δ9-THC also transiently activates and desensitizes the transient receptor potential (TRP) channels TRPA1, TRPV1, and TRPV2 [97][98][99]. Given the synergistic relation between seizures and inflammation [100][101][102], the cannabinoid system provides a novel strategy to target both segments of this feedback cycle.…”

Section: δ9-thcmentioning

confidence: 99%

Cannabinoids and Epilepsy

et al. 2015

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Cannabis has been used for centuries to treat seizures. Recent anecdotal reports, accumulating animal model data, and mechanistic insights have raised interest in cannabisbased antiepileptic therapies. In this study, we review current understanding of the endocannabinoid system, characterize the pro-and anticonvulsive effects of cannabinoids [e.g., Δ9-tetrahydrocannabinol and cannabidiol (CBD)], and highlight scientific evidence from pre-clinical and clinical trials of cannabinoids in epilepsy. These studies suggest that CBD avoids the psychoactive effects of the endocannabinoid system to provide a well-tolerated, promising therapeutic for the treatment of seizures, while whole-plant cannabis can both contribute to and reduce seizures. Finally, we discuss results from a new multicenter, open-label study using CBD in a population with treatment-resistant epilepsy. In all, we seek to evaluate our current understanding of cannabinoids in epilepsy and guide future basic science and clinical studies.

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“…Finally, it is increasingly recognized that proinflammatory molecules released by glia contribute to some of the acquired channelopathies described in epilepsy by inducing alterations in voltage-and receptor-gated ion channels via either post-translational or transcriptional mechanisms [reviewed by (Vezzani et al, 2011b;Viviani et al, 2004)]. …”

Section: Functional Consequences Of Astrocyte-mediated Brain Inflammamentioning

confidence: 99%

Astrocyte immune responses in epilepsy

Aronica

Ravizza

Zurolo

et al. 2012

Glia

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Astrocytes, the major glial cell type of the central nervous system (CNS), are known to play a major role in the regulation of the immune/inflammatory response in several human CNS diseases. In epilepsy-associated pathologies, the presence of astrogliosis has stimulated extensive research focused on the role of reactive astrocytes in the pathophysiological processes that underlie the development of epilepsy. In brain tissue from patients with epilepsy, astrocytes undergo significant changes in their physiological properties, including the activation of inflammatory pathways. Accumulating experimental evidence suggests that proinflammatory molecules can alter glio-neuronal communications contributing to the generation of seizures and seizure-related neuronal damage. In particular, both in vitro and in vivo data point to the role of astrocytes as both major source and target of epileptogenic inflammatory signaling. In this context, understanding the astroglial inflammatory response occurring in epileptic brain tissue may provide new strategies for targeting astrocyte-mediated epileptogenesis. This article reviews current evidence regarding the role of astrocytes in the regulation of the innate immune responses in epilepsy. Both clinical observations in drug-resistant human epilepsies and experimental findings in clinically relevant models will be discussed and elaborated, highlighting specific inflammatory pathways (such as interleukin-1b/toll-like receptor 4) that could be potential targets for antiepileptic, disease-modifying therapeutic strategies. V

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The role of inflammation in epilepsy

Cited by 1,545 publications

References 178 publications

Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice

Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice

Cannabinoids and Epilepsy

Astrocyte immune responses in epilepsy

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