Immunohistochemical localization of interleukin-1β, interleukin-1 receptor antagonist and interleukin-1β converting enzyme/caspase-1 in the rat brain after peripheral administration of kainic acid

Eriksson, Charlotta; Dam, Anne Marie Van; Lucassen, Paul J.; Bol, John G.J.M.; Winblad, Bengt; Schultzberg, Marianne

doi:10.1016/s0306-4522(99)00178-5

Cited by 127 publications

(93 citation statements)

References 115 publications

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“…Experimental seizures in rodents induce inflammatory processes in brain regions in which epileptic activity originates and spreads [1,2]; in this respect, the activation of the interleukin (IL)-1β/IL-1 receptor type 1 (R1) signaling in glia and neurons is a key event contributing to intrinsic brain inflammation [3][4][5][6][7][8][9][10][11][12]. Paracrine and autocrine activation of this signaling by the brain application of IL-1β exacerbates kainic acid-or bicuculline-induced seizures in rats and mice [5,11,13], and lowers the seizure threshold in febrile seizure models [7,8].…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

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

et al. 2011

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Section: Il-1β and Hmgb1 Expression In Seizuresmentioning

confidence: 99%

“…Following seizures, IL-1β and HMGB1 are primarily expressed in microglia, although HMGB1 is also found in neurons [23,24]. IL-1β and IL-1R1 are up-regulated as a result of seizures in a variety of experimental models, including those induced by electrical stimulation, kainate, bicuculline, and hyperthermia [23,[25][26][27]. Elevated IL-1β and IL-1R1 have also been observed in brain tissue from patients with temporal lobe epilepsy and hippocampal sclerosis, and elevated IL-1β has been reported in cerebrospinal fluid (CSF) from children with febrile seizures [28,29].…”

Section: Il-1β and Hmgb1 Expression In Seizuresmentioning

confidence: 99%

Epilepsy and the inflammasome: Targeting inflammation as a novel therapeutic strategy for seizure disorders

Edye¹,

Walker²,

Sills³

et al. 2014

Inflammasome

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Epilepsy is the most common serious brain disorder worldwide. Recent evidence from experimental models of epilepsy and clinical brain tissue from epilepsy surgery suggests inflammation may play a pathological role in this disorder. Activation of a multimolecular protein complex termed the ‘inflammasome’ occurs during inflammation to drive the innate immune response. Inflammasome activation, with release of inflammatory mediators including interleukin-1β and high-mobility group box-1, may play a crucial role in the development of epilepsy (epileptogenesis) after brain insult. Immunomodulatory drugs targeting the inflammasome pathway may represent a novel antiepileptogenic treatment strategy for epilepsy. This review summarises the current literature surrounding inflammasome activation and epilepsy.

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“…A similar inflammatory reaction has also been reported in experimental models of temporal lobe epilepsy. In particular, an increase of proinflammatory cytokines and of markers of the innate immunity (IL-1␤, IL-6, TNF-␣, NF-B system, COX-2, prostaglandins, and Toll-like receptors) has been detected in the rat hippocampus, starting within the first hour after the induction of a status epilepticus (SE) and lasting several days (Eriksson et al, 1999;De Simoni et al, 2000;Vezzani et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Status Epilepticus Induces a Particular Microglial Activation State Characterized by Enhanced Purinergic Signaling

Avignone¹,

Ulmann²,

Levavasseur³

et al. 2008

J. Neurosci.

253

285

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Microglia cells are the resident macrophages of the CNS, and their activation plays a critical role in inflammatory reactions associated with many brain disorders, including ischemia, Alzheimer's and Parkinson's diseases, and epilepsy. However, the changes of microglia functional properties in epilepsy have rarely been studied. Here, we used a model of status epilepticus (SE) induced by intraperitoneal kainate injections to characterize the properties of microglial cells in hippocampal slices from CX3CR1 eGFP/ϩ mice. SE induced within 3 h an increased expression of inflammatory mediators in the hippocampus, followed by a modification of microglia morphology, a microglia proliferation, and a significant neurodegeneration in CA1. Changes in electrophysiological intrinsic membrane properties of hippocampal microglia were detected at 24 -48 h after SE with, in particular, the appearance of new voltage-activated potassium currents. Consistent with the observation of an upregulation of purinergic receptor mRNAs in the hippocampus, we also provide pharmacological evidence that microglia membrane currents mediated by the activation of P2 receptors, including P2X 7 , P2Y 6 , and P2Y 12 , were increased 48 h after SE. As a functional consequence of this modification of purinergic signaling, motility of microglia processes toward a source of P2Y 12 receptor agonist was twice as fast in the epileptic hippocampus. This study is the first functional description of microglia activation in an in vivo model of inflammation and provides evidence for the existence of a particular microglial activation state after a status epilepticus.

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Immunohistochemical localization of interleukin-1β, interleukin-1 receptor antagonist and interleukin-1β converting enzyme/caspase-1 in the rat brain after peripheral administration of kainic acid

Cited by 127 publications

References 115 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

Epilepsy and the inflammasome: Targeting inflammation as a novel therapeutic strategy for seizure disorders

Status Epilepticus Induces a Particular Microglial Activation State Characterized by Enhanced Purinergic Signaling

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