Protective effects of interleukin-10 on the development of epileptiform activity evoked by transient episodes of hypoxia in rat hippocampal slices

Levin, S. G.; Godukhin, O. V.

doi:10.1007/s11055-007-0036-1

Cited by 24 publications

(17 citation statements)

References 16 publications

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“…Proinflammatory cytokines are known to play a critical role in the pathogenesis of TLE (Moore et al, 2001 ; Vezzani et al, 2002 ; Li et al, 2011 ). A number of animal studies and clinical observations suggest an anticonvulsant effect of IL-10 (Kurreeman et al, 2004 ; Levin and Godukhin, 2007 ; Ishizaki et al, 2009 ; Youn et al, 2012 ). A recent analysis indicated neuroprotective effects of IL-10 against the development of hypoxia-evoked epileptiform activity in rat hippocampal slices (Levin and Godukhin, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

“…A number of animal studies and clinical observations suggest an anticonvulsant effect of IL-10 (Kurreeman et al, 2004 ; Levin and Godukhin, 2007 ; Ishizaki et al, 2009 ; Youn et al, 2012 ). A recent analysis indicated neuroprotective effects of IL-10 against the development of hypoxia-evoked epileptiform activity in rat hippocampal slices (Levin and Godukhin, 2007 ). In experimental hyperthermic seizures in rat models, the seizure threshold temperature in IL-10 treated rats was significantly upregulated compared to normal controls (Ishizaki et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

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Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy

Alsharafi

Xiao

Abuhamed

et al. 2015

Front. Cell. Neurosci.

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Accumulating evidence is emerging that microRNAs (miRNAs) are key regulators in controlling neuroinflammatory responses that are known to play a potential role in the pathogenesis of temporal lobe epilepsy (TLE). The aim of the present study was to investigate the dynamic expression pattern of interleukin (IL)-10 as an anti-inflammatory cytokine and miR-187 as a post-transcriptional inflammation-related miRNA in the hippocampus of a rat model of status epilepticus (SE) and patients with TLE. We performed a real-time quantitative PCR and western blot on rat hippocampus 2 h, 7 days, 21 days and 60 days following pilocarpine-induced SE, and on hippocampus obtained from TLE patients and normal controls. To detect the relationship between IL-10 and miR-187 on neurons, lipopolysaccharide (LPS) and IL-10-stimulated neurons were performed. Furthermore, we identified the effect of antagonizing miR-187 by its antagomir on IL-10 secretion. Here, we reported that IL-10 secretion and miR-187 expression levels are inversely correlated after SE. In patients with TLE, the expression of IL-10 was also significantly upregulated, whereas miR-187 expression was significantly downregulated. Moreover, miR-187 expression was significantly reduced following IL-10 stimulation in an IL-10–dependent manner. On the other hand, antagonizing miR-187 promoted the production of IL-10 in hippocampal tissues of rat model of SE. Our findings demonstrate a critical role of miR-187 in the physiological regulation of IL-10 anti-inflammatory responses and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, modulation of the IL-10 / miR-187 axis may be a new therapeutic approach for TLE.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy

Alsharafi

Xiao

Abuhamed

et al. 2015

Front. Cell. Neurosci.

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“…Suppression of miR‐187 using an antagomir during the first hours after status epilepticus increased levels of IL‐10 in the early phases of epileptogenesis (Alsharafi et al, ). IL‐10 has an anti‐convulsant effect in models of hypoxic ischemic‐induced seizures and febrile seizures (Levin and Godukhin, ; Ishizaki et al, ), and is known to provide trophic support to neurons. While not tested in this study, antagonizing miR‐187 in the acute and latent phase after status epilepticus may provide neuroprotection through up‐regulation of IL‐10, and may thus be a desirable target to prevent spontaneous recurrent seizures after an epileptogenic insult.…”

Section: Micrornas Regulating Inflammation In Epilepsy and Epileptogementioning

confidence: 99%

MicroRNA‐induced silencing in epilepsy: Opportunities and challenges for clinical application

Tiwari

Peariso

Groß

2017

Developmental Dynamics

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MicroRNAs are master regulators of gene expression. Single microRNAs influence multiple proteins within diverse molecular pathways and networks. Therefore, changes in levels or activity of microRNAs can have profound effects on cellular function. This makes dysregulated microRNA-induced silencing an attractive potential disease mechanism in complex disorders like epilepsy, where numerous cellular pathways and processes are affected simultaneously. Indeed, several years of research in rodent models have provided strong evidence that acute or recurrent seizures change microRNA expression and function. Moreover, altered microRNA expression has been observed in brain and blood from patients with various epilepsy disorders, such as tuberous sclerosis. MicroRNAs can be easily manipulated using sense or antisense oligonucleotides, opening up opportunities for therapeutic intervention. Here, we summarize studies using these techniques to identify microRNAs that modulate seizure susceptibility, describe protein targets mediating some of these effects, and discuss cellular pathways, for example neuroinflammation, that are controlled by epilepsy-associated microRNAs. We critically assess current gaps in knowledge regarding target-and cell-specificity of microRNAs that have to be addressed before clinical application as therapeutic targets or biomarkers. The recent progress in understanding microRNA function in epilepsy has generated strong momentum to encourage in-depth mechanistic studies to develop microRNA-targeted therapies. Developmental Dynamics 247:94-110, 2018. V C 2017 Wiley Periodicals, Inc.

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“…Indeed, IL-10 deactivates macrophages, which in turn decreases the production of cytokines by T cells (Youn, 2013). Several animal studies and clinical observations suggest an anticonvulsant effect of IL-10; one report showed protective effects of IL-10 against the development of epileptiform activity evoked by transient episodes of hypoxia in rat hippocampal slices (Levin and Godukhin, 2007). Production of IL-10 in blood is controversial; some authors reported no differences in plasma IL-10 between patients with focal seizure and control (Virta et al, 2002), whereas IL-10 production was significantly lower in patients suffering from focal seizure than in healthy control (Li et al, 2011).…”

Section: Cytokines and Ros/rsn In Cultured Pbmcmentioning

confidence: 99%

Milk from different species: Relationship between protein fractions and inflammatory response in infants affected by generalized epilepsy

Albenzio

Santillo

Ciliberti

et al. 2016

Journal of Dairy Science

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The present study was undertaken to evaluate the effect of protein fractions from bovine, caprine, and ovine milk on production of cytokines and reactive oxygen species (ROS) and reactive nitrogen species (RNS) by cultured peripheral blood mononuclear cells (PMBC) from infants with generalized epilepsy. Bovine, caprine, and ovine bulk milks were pasteurized and analyzed for chemical composition. Then, PBMC were isolated from 10 patients with generalized epilepsy (5 males; mean age 33.6±5.4mo). Production of tumor necrosis factor-α (TNF-α), IL-10, IL-6, and IL-1β was studied in cultured PBMC (from infants with epilepsy and controls) stimulated by bovine, caprine, and ovine milk and casein and whey protein fractions, and levels of ROS and RNS were measured in the culture supernatant. The ability of PBMC to secrete cytokines in response to milk and protein fraction stimulation may predict the secretion of soluble factor TNF-α in the bloodstream of challenged patients. Bovine, caprine, and ovine bulk milks induced low-level production of IL-10 by cultured PBMC in at least 50% of cases; the same behavior was observed in both casein and whey protein fractions for all species studied. Bovine and ovine milk and their casein fractions induced production of lower levels of IL-1β in 80% of patients, whereas caprine milk and its casein fraction induced the highest levels in 80% of patients. The amount of IL-6 detected after stimulation of PBMC by milk and its fractions for all species was lower than that of other proinflammatory cytokines. In the bovine, total free radicals were higher in bulk milk and lower in the casein fraction, whereas the whey protein fraction showed an intermediate level; in caprine, ROS/RNS levels were not different among milk fractions, whereas ovine had higher levels for bulk milk and casein than the whey protein fraction. Lower levels of ROS/RNS detected in PBMC cultured with caprine milk fraction could be responsible for the lower levels of TNF-α cytokine in the corresponding fraction. Cytokines might be useful biomarkers to discriminate the effects of foods on the inflammatory response; dietary strategies could help in alleviating the negative effects of epilepsy in infants.

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Protective effects of interleukin-10 on the development of epileptiform activity evoked by transient episodes of hypoxia in rat hippocampal slices

Cited by 24 publications

References 16 publications

Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy

Correlation Between IL-10 and microRNA-187 Expression in Epileptic Rat Hippocampus and Patients with Temporal Lobe Epilepsy

MicroRNA‐induced silencing in epilepsy: Opportunities and challenges for clinical application

Milk from different species: Relationship between protein fractions and inflammatory response in infants affected by generalized epilepsy

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