The Effects of Interleukin-10 on the Development of Epileptiform Activity in the Hippocampus Induced by Transient Hypoxia, Bicuculline, and Electrical Kindling

Abstract

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.

Insights from Zebrafish and Mouse Models on the Activity and Safety of Ar-Turmerone as a Potential Drug Candidate for the Treatment of Epilepsy

“…BDNF also plays a role in the pathogenesis of temporal lobe epilepsy (TLE) by enhancing neuronal outgrowth and mossy fiber sprouting [43]. IL10 prevents neuronal damage caused by excess of excitatory neurotransmitters and reduces the harmful effects of hypoxia as well [80]. Our results show a significant decrease in c-fos transcription in larvae treated with ar-turmerone and exposed to PTZ.…”

Inflammation in epileptogenesis after traumatic brain injury

“…Pre-synaptic NMDA receptors are agonists for Ca 2+ -mediated glutamate release, and when activated by inflammatory factors such as IL-1β and HMGB1 can cause an excess of intracellular Ca 2+ leading to an extracellular hyperexcitability and excitotoxicity [95]. Several other cytokines including TNF-α and IL-10 have also been associated with the regulation of seizure duration in experimental kindling models [97, 98]. Though these correlations have been seen in multiple studies with different models, the mechanisms underlying the relationship between the inflammatory environment and epileptogenesis, particularly in the context of brain injury, remain still poorly understood.…”

PI3Kγ deficiency enhances seizures severity and associated outcomes in a mouse model of convulsions induced by intrahippocampal injection of pilocarpine

“…Godukhin et al (2009) demonstrated that intrahippocampal injections of IL-10 suppressed the development of focal ictal discharges. This indicates a protective role of this cytokine in the early stages of seizures, an effect that could be lost in the absence of PI3Kγ.…”