The Effects of Interleukin-10 on the Development of Epileptiform Activity in the Hippocampus Induced by Transient Hypoxia, Bicuculline, and Electrical Kindling
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia. Neuroscience and Behavioral Physiology
10/2009; 39(7):625-31. DOI: 10.1007/s11055-009-9187-6
The comparative effects of the anti-inflammatory cytokine interleukin-10 on the development of epileptiform activity were studied in hippocampal field CA1 neurons in different models of epileptogenesis not accompanied by visible morphological lesions in brain cells: 1) a model of hypoxic kindling in rat hippocampal slices; 2) a disinhibitory model of epileptogenesis in rat hippocampal slices using the GABAA receptor blocker bicuculline; and 3) a partial electrical kindling model in intact rats. Interleukin-10 (1 ng/ml) blocked the development of post-hypoxic hyperexcitability of field CA1 pyramidal neurons in hippocampal slices, decreasing the effectiveness of hypoxia in suppressing neuron activity during the hypoxic episode. Interleukin-10 had no effect on the initiation of epileptiform activity in pyramidal neurons induced by the proconvulsant bicuculline. Single intrahippocampal injections of interleukin-10 at a dose of 1 ng in 5 microl suppressed the development of focal convulsions ("ictal" discharges) at the stimulation site in partial kindling in freely moving animals for several hours after administration. However, this cytokine had no effect on the duration of the "interictal" component of focal afterdischarges or on the severity of behavioral seizures. These results show that the anti-inflammatory cytokine interleukin-10, at the concentrations used here, has not only antihypoxic activity, but also a protective effect in relation to the initiation of the "ictal," but not the "interictal" component of epileptiform activity in hippocampal neurons.
Available from: Tatiana Afrikanova
- "BDNF also plays a role in the pathogenesis of temporal lobe epilepsy (TLE) by enhancing neuronal outgrowth and mossy fiber sprouting . IL10 prevents neuronal damage caused by excess of excitatory neurotransmitters and reduces the harmful effects of hypoxia as well . Our results show a significant decrease in c-fos transcription in larvae treated with ar-turmerone and exposed to PTZ. "
[Show abstract] [Hide abstract]
ABSTRACT: In a previous study, we uncovered the anticonvulsant properties of turmeric oil and its sesquiterpenoids (ar-turmerone, α-, β-turmerone and α-atlantone) in both zebrafish and mouse models of chemically-induced seizures using pentylenetetrazole (PTZ). In this follow-up study, we aimed at evaluating the anticonvulsant activity of ar-turmerone further. A more in-depth anticonvulsant evaluation of ar-turmerone was therefore carried out in the i.v. PTZ and 6-Hz mouse models. The potential toxic effects of ar-turmerone were evaluated using the beam walking test to assess mouse motor function and balance. In addition, determination of the concentration-time profile of ar-turmerone was carried out for a more extended evaluation of its bioavailability in the mouse brain. Ar-turmerone displayed anticonvulsant properties in both acute seizure models in mice and modulated the expression patterns of two seizure-related genes (c-fos and brain-derived neurotrophic factor [bdnf]) in zebrafish. Importantly, no effects on motor function and balance were observed in mice after treatment with ar-turmerone even after administering a dose 500-fold higher than the effective dose in the 6-Hz model. In addition, quantification of its concentration in mouse brains revealed rapid absorption after i.p. administration, capacity to cross the BBB and long-term brain residence. Hence, our results provide additional information on the anticonvulsant properties of ar-turmerone and support further evaluation towards elucidating its mechanism of action, bioavailability, toxicity and potential clinical application.
PLoS ONE 12/2013; 8(12):e81634. DOI:10.1371/journal.pone.0081634 · 3.23 Impact Factor
Available from: PubMed Central
- "Inhibitors of IL-1-converting enzyme/Caspase-1 and antagonists of IL-1β receptors showed strong anticonvulsant activity in seizure models , while exogenous IL-1β has pro-convulsive properties. Drugs that block the IL-1β actions had entered clinical trials as potential therapeutics for autoimmune and inflammatory pathologies, and may also have therapeutic potential in epilepsies associated with pro-inflammatory processes in the brain [143, 144]. Resveratrol, a TLR3 antagonist, reduced the frequency of video-monitored spontaneous seizures in rats after daily administration from day1 to day10 after KA-induced SE . "
[Show abstract] [Hide abstract]
ABSTRACT: Until recently, epilepsy medical therapy is usually limited to anti-epileptic drugs (AEDs). However, approximately 1/3 of epilepsy patients, described as drug-resistant epilepsy (DRE) patients, still suffer from continuous frequent seizures despite receiving adequate AEDs treatment of sufficient duration. More recently, with the remarkable progress of immunology, immunity and inflammation are considered to be key elements of the pathobiology of epilepsy. Activation of inflammatory processes in brain tissue has been observed in both experimental seizure animal models and epilepsy patients. Anti-inflammatory and immunotherapies also showed significant anticonvulsant properties both in clinical and in experimental settings. The above emerging evidence indicates that modulation of immunity and inflammatory processes could serve as novel specific targets to achieve potential anticonvulsant effects for the patients with epilepsy, especially DRE. Herein we review the recent evidence supporting the role of inflammation in the development and perpetuation of seizures, and also discuss the recent achievements in modulation of inflammation and immunotherapy applied to the treatment of epilepsy. Apart from medical therapy, we also discuss the influences of surgery, ketogenic diet, and electroconvulsive therapy on immunity and inflammation in DRE patients. Taken together, a promising perspective is suggested for future immunomodulatory therapies in the treatment of patients with DRE.
Current Neuropharmacology 01/2013; 11(1):114-27. DOI:10.2174/157015913804999540 · 3.05 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Mesial temporal lobe epilepsy (MTLE) is a common neurological disorder characterized by hyperexcitability of limbic structures. Studies in epileptic patients and animal models of MTLE indicate that epileptiform activity arise primarily from limbic areas (e.g. hippocampus) with secondary propagation to cortical areas. A wealth of evidence indicates that epileptiform activity is associated with complex patterns in the expression and function of ion channels, receptors and transporters. Accordingly, several studies portrait MTLE as a post-transcriptional acquired channelopathy. The present review describes the most common features of epileptiform activity emerging from animal models of limbic epileptogenesis and critically discusses the supporting evidence that MTLE is a complex acquired channelopathy.
Frontiers in bioscience (Scholar edition) 01/2011; 3(2):565-93.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.