Lack of Association Between an Interleukin 1 Beta (IL-1β) Gene Variation and Refractory Temporal Lobe Epilepsy

We aimed to investigate the role of interleukin-1 beta (IL-1β) in the mechanisms underlying mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE+HS). We assessed a cohort of 194 patients with MTLE+HS and 199 healthy controls. Patients were divided into those with positive and negative antecedent febrile seizures (FS). We used a multidimensional approach, including (i) genetic association with single nucleotide polymorphisms (SNPs) in the IL1B gene; (ii) quantification of the IL1B transcript in the hippocampal tissue of patients with refractory seizures; and (iii) quantification of the IL-1β protein in the plasma. We found a genetic association signal for two SNPs, rs2708928 and rs3730364*C in the IL1B gene, regardless of the presence of FS (adjusted p = 9.62e–11 and 5.14e–07, respectively). We found no difference between IL1B transcript levels when comparing sclerotic hippocampal tissue from patients with MTLE+HS, without FS, and hippocampi from autopsy controls (p > 0.05). Nevertheless, we found increased IL-1β in the plasma of patients with MTLE+HS with FS compared with controls (p = 0.0195). Our results support the hypothesis of a genetic association between MTLE+HS and the IL1B gene

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GABABR1 (G1465A) gene variation and temporal lobe epilepsy controversy: New evidence

Seizure ◽

10.1016/j.seizure.2007.12.006 ◽

2008 ◽

Vol 17 (6) ◽

pp. 567-571 ◽

Cited By ~ 8

Author(s):

Marcelo Andrés Kauffman ◽

Estrella Mariel Levy ◽

Damian Consalvo ◽

José Mordoh ◽

Silvia Kochen

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Gene Variation ◽

New Evidence

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Interleukin-1? gene polymorphism and susceptibility to temporal lobe epilepsy with hippocampal sclerosis

Annals of Neurology ◽

10.1002/1531-8249(200012)48:6<948::aid-ana21>3.0.co;2-g ◽

2000 ◽

Vol 48 (6) ◽

pp. 948-949 ◽

Cited By ~ 30

Author(s):

Armin Heils ◽

Karsten Haug ◽

Wolfram S. Kunz ◽

Guillen Fernandez ◽

Steve Horvath ◽

...

Keyword(s):

Gene Polymorphism ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Interleukin 1

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Anakinra Reduces Epileptogenesis, Provides Neuroprotection, and Attenuates Behavioral Impairments in Rats in the Lithium–Pilocarpine Model of Epilepsy

Pharmaceuticals ◽

10.3390/ph13110340 ◽

2020 ◽

Vol 13 (11) ◽

pp. 340

Author(s):

Alexandra V. Dyomina ◽

Olga E. Zubareva ◽

Ilya V. Smolensky ◽

Dmitry S. Vasilev ◽

Maria V. Zakharova ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Excitatory Amino Acid ◽

Neuroprotective Effect ◽

Interleukin 1 ◽

Chronic Phase ◽

Marker Genes ◽

Excitatory Amino Acid Transporter ◽

Pilocarpine Model ◽

Behavioral Impairments

Temporal lobe epilepsy is a widespread chronic disorder that manifests as spontaneous seizures and is often characterized by refractoriness to drug treatment. Temporal lobe epilepsy can be caused by a primary brain injury; therefore, the prevention of epileptogenesis after a primary event is considered one of the best treatment options. However, a preventive treatment for epilepsy still does not exist. Neuroinflammation is directly involved in epileptogenesis and neurodegeneration, leading to the epileptic condition and cognitive decline. In the present study, we aimed to clarify the effect of treatment with a recombinant form of the Interleukin-1 receptor antagonist (anakinra) on epileptogenesis and behavioral impairments in rats using the lithium–pilocarpine model. We found that anakinra administration during the latent phase of the model significantly suppressed the duration and frequency of spontaneous recurrent seizures in the chronic phase. Moreover, anakinra administration prevented some behavioral impairments, including motor hyperactivity and disturbances in social interactions, during both the latent and chronic periods. Histological analysis revealed that anakinra administration decreased neuronal loss in the CA1 and CA3 areas of the hippocampus but did not prevent astro- and microgliosis. The treatment increased the expression level of the solute carrier family 1 member 2 gene (Slc1a2, encoding excitatory amino acid transporter 2 (EAAT2)) in the hippocampus, potentially leading to a neuroprotective effect. However, the increased gene expression of proinflammatory cytokine genes (Interleukin-1β (Il1b) and tumor necrosis factor α (Tnfa)) and astroglial marker genes (glial fibrillary acidic protein (Gfap) and inositol 1,4,5-trisphosphate receptor type 2 (Itpr2)) in experimental rats was not affected by anakinra treatment. Thus, our data demonstrate that the administration of anakinra during epileptogenesis has some beneficial disease-modifying effects.

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Lack of GABABR1 gene variation (G1465A) in a Chinese population with temporal lobe epilepsy

Seizure ◽

10.1016/j.seizure.2005.09.009 ◽

2005 ◽

Vol 14 (8) ◽

pp. 611-613 ◽

Cited By ~ 6

Author(s):

Liankun Ren ◽

Liri Jin ◽

Boyu Zhang ◽

Yanbin Jia ◽

Liwen Wu ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Chinese Population ◽

Gene Variation

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Methylation pattern in the promoter region of interleukin 1-β gene in animal models of mesial temporal lobe epilepsy induced by pilocarpine injection

10.19146/pibic-2015-37485 ◽

2015 ◽

Author(s):

Iscia Teresinha Lopes Cendes ◽

Larissa Silva Antunes De Carvalho

Keyword(s):

Animal Models ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Promoter Region ◽

Interleukin 1 ◽

Mesial Temporal Lobe Epilepsy ◽

Methylation Pattern ◽

Mesial Temporal Lobe ◽

Pilocarpine Injection

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Value of Functionalized Superparamagnetic Iron Oxide Nanoparticles in the Diagnosis and Treatment of Acute Temporal Lobe Epilepsy on MRI

Neural Plasticity ◽

10.1155/2016/2412958 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 9

Author(s):

Tingting Fu ◽

Qingxia Kong ◽

Huaqiang Sheng ◽

Lingyun Gao

Keyword(s):

Iron Oxide ◽

Temporal Lobe Epilepsy ◽

Iron Oxide Nanoparticles ◽

Temporal Lobe ◽

Interleukin 1 ◽

Superparamagnetic Iron Oxide ◽

Superparamagnetic Iron Oxide Nanoparticles ◽

Brain Inflammation ◽

Oxide Nanoparticles ◽

Epileptogenic Zone

Purpose.Although active targeting of drugs using a magnetic-targeted drug delivery system (MTDS) with superparamagnetic iron oxide nanoparticles (SPIONs) is a very effective treatment approach for tumors and other illnesses, successful results of drug-resistant temporal lobe epilepsy (TLE) are unprecedented. A hallmark in the neuropathology of TLE is brain inflammation, in particular the activation of interleukin-1β(IL-1β) induced by activated glial cells, which has been considered a new mechanistic target for treatment. The purpose of this study was to determine the feasibility of the functionalized SPIONs with anti-IL-1βmonoclonal antibody (mAb) attached to render MRI diagnoses and simultaneously provide targeted therapy with the neutralization of IL-1βoverexpressed in epileptogenic zone of an acute rat model of TLE.Experimental Design.The anti-IL-1βmAb-SPIONs were studied in vivo versus plain SPIONs and saline. Lithium-chloride pilocarpine-induced TLE models (n=60) were followed by Western blot, Perl’s iron staining, Nissl staining, and immunofluorescent double-label staining after MRI examination.Results.The magnetic anti-IL-1βmAb-SPION administered intravenously, which crossed the BBB and was concentrated in the astrocytes and neurons in epileptogenic tissues, rendered these tissues visible on MRI and simultaneously delivered anti-IL-1βmAb to the epileptogenic focus.Conclusions.Our study provides the first evidence that the novel approach enhanced accumulation and the therapeutic effect of anti-IL-1βmAb by MTDS using SPIONs.

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