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 μl 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.
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References
O. V. Godukhin, “Role of cytokines in the development of convulsive activity in the brain,” Zh. Vyssh. Nerv. Deyat., 54, No. 4, 407–418 (2007).
S. G. Levin and O. V. Godukhin, “Protective effect of IL-10 on the development of epileptiform activity evoked by transient episodes of hypoxia in rat hippocampal slices,” Zh. Vyssh. Nerv. Deyat., 56, No. 3, 379–383 (2006).
J. A. Aarli, “Epilepsy and the immune system,” Arch. Neurol., 57, 1689–1692 (2000).
M. Avoli, M. D’Antuono, J. Louvel, R. Kohling, G. Biagini, R. Pumain, G. D’Arcangelo, and V. Tancredi, “Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro,” Progr. Neurobiol., 68, 167–207 (2002).
A. Bachis, A. M. Colangelo, S. Vicini, P. P. Doe, M. A. De-Bernardi, G. Brooker, and I. Mocchetti, “Interleukin-10 prevents glutamate-mediated cerebellar granule cell death by blocking caspase-3 like activity,” J. Neurosci., 21, 3104–3112 (2001).
M. E. Burkovetskaya, S. G. Levin, and O. V. Godukhin, “Neuroprotective effects of interleukin-10 and tumor necrosis factor-alpha against hypoxia-induced hyperexcitability in hippocampal slice neurons,” Neurosci. Lett., 416, 236–240 (2007).
M. G. De Simoni, C. Perego, T. Ravizza, D. Moneta, M. Conti, F. Marchesi, A. De Luigi, S. Garattini, and A. Vezzani, “Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus,” Eur. J. Neurosci., 12, No. 7, 2623–2633 (2000).
T. De Smedt, K. Vonck, R. Raedt, S. Dedeurwaerdere, P. Claeys, B. Legros, T. Wyckhuys,W. Wadman, and P. Boon, “Rapid kindling in preclinical anti-epileptic drug development: the effect of levetiracetam,” Epilepsy Res., 67, 109–116 (2005).
V. Dzhala and K. J. Staley, “Transition from interictal to ictal activity in limbic networks in vitro,” J. Neurosci., 23, No. 21, 7873–7880 (2003).
O. Godukhin, A. Savin, S. Kalemenev, and S. Levin, “Neuronal hyperexcitability induced by repeated brief episodes of hypoxia in rat hippocampal slices: involvement of ionotropic glutamate receptors and L-type Ca2+ channels,” Neuropharmacology, 42, 459–466 (2002).
K. R. Goldstein, R. Bhatt, B. E. Barton, S. S. Zalcman, P. Rameshwar, and A. Siegel, “Effects of hemispheric lateralization and site specificity on immune alterations induced by kindled temporal lobe seizures,” Brain Behav. Immun., 16, No. 6, 706–719 (2002).
D. S. Hewapathirane and W. M. Burnham, “Propagation of amygdale-kindled seizures to the hippocampus in the rat: electroencephalographic features and behavioural correlates,” Neurosci. Res., 53, 369–375 (2005).
J. L. Jankowsky and P. H. Patterson, “The role of cytokines and growth factors in seizures and their sequelae,” Progr. Neurobiol., 63, 125–149 (2001).
M. S. Jensen and Y. Yaari, “Role of intrinsic burst firing, potassium accumulation, and electrical coupling in the elevated potassium model of hippocampal epilepsy,” J. Neurophysiol., 77, 1224–1233 (1997).
S. M. Knoblach and A. I. Faden, “Interleukin-10 improves outcome and alters proinflammatory cytokine expression after experimental traumatic brain injury,” Exptl. Neurol., 153, 143–151 (1998).
D. C. McIntyre, J. R. Plant, and M. E. Kelly, “Dorsal hippocampal kindling produces long-lasting changes in the origin of spontaneous discharges in the piriform versus perirhinal cortex in vitro,” Epilepsy Res., 39, 191–200 (2000).
L. J. Pellegrino, A. S. Pellegrino, and A. J. Cushman, A Stereotaxic Atlas of the Rat Brain, Plenum Press, New York (1979).
R. J. Racine, “Modification of seizure activity by electrical stimulation: II. Motor seizure,” EEG Clin. Neurophysiol., 32, 281–294 (1972).
H. Schneider, F. Pitossi, D. Balschun, A. Wagner, A. del Rey, and H. O. Besedovsky, “A neuromodulatory role of interleukin-lβ in the hippocampus,” Proc. Natl. Acad. Sci. USA, 95, 7778–7783 (1998).
P. A. Spera, J. A. Ellison, G. Z. Feuerstein, and F. C. Barone, “IL-10 reduces rat brain injury following focal stroke,” Neurosci. Lett., 251, No. 3, 189–192 (1998).
R. Straussberg, J. Amir, L. Harel, I. Punsky, and H. Bessler, “Proand anti-inflammatory cytokines in children with febrile convulsions,” Pediatr. Neurol., 24, 49–53 (2001).
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Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 58, No. 3, pp. 351–358, May–June, 2008.
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Godukhin, O.V., Levin, S.G. & Parnyshkova, E.Y. The Effects of Interleukin-10 on the Development of Epileptiform Activity in the Hippocampus Induced by Transient Hypoxia, Bicuculline, and Electrical Kindling. Neurosci Behav Physi 39, 625–631 (2009). https://doi.org/10.1007/s11055-009-9187-6
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DOI: https://doi.org/10.1007/s11055-009-9187-6