The involvement of proinflammatory cytokines in the pathogenesis of audiogenic epilepsy

封面

如何引用文章

全文:

详细

Epilepsy is a heterogeneous disease, which determines the relevance of investigating the mechanisms of pathogenesis of its various types, including reflex epilepsy. Pharmacotherapy is common for the treatment of patients with epilepsy, however, despite the significant recent achievements, 20-30% of patients remain resistant to the ongoing treatment. The urgency of creating new antiepileptic drugs, in particular, immune ones is due not only to a significant proportion of pharmacoresistant cases, but also to the struggle for the quality of life of patients. The neuroinflammation system in animals with different genetically determined audiogenic epilepsy proneness was investigated. These genetic groups were Krushinsky–Molodkina rats (tonic seizures of maximum intensity in response to the action of sound) and “0” strain (control group, non-convulsive phenotype). The main proinflammatory cytokines levels in the dorsal striatum and brain stem in rats of these genetic groups were measured by multiplex immunofluorescence assay. Background levels of IL-1â, IL-6 and TNFá in the dorsal striatum of KM rats were significantly lower than in the control “0” strain rats, whereas in the brain stem in the “background” levels of these metabolites did not differ. Four hours after the sound exposure, the TNFá level in the dorsal striatum of KM rats was significantly lower than in “0” rats. In KM rats, after the sound exposure and subsequent tonic seizures, the levels of IL-1â and IL-6 in the dorsal striatum were significantly higher than in the background. The IL-2 content was not detected in the background in KM rats, whereas after audiogenic seizures its level was 14.01 pg/ml. In the brain stem of KM rats, the levels of IL-1â and TNFá after audiogenic seizures were significantly lower than in the background. In rats of the “0” strain, cytokine levels in the dorsal striatum after the sound exposure did not differ from those in the background, while IL-1ß levels in their brain stem were significantly lower than the background state. Particular modulating role of the studied proinflammatory cytokines in the pathogenesis of audiogenic epilepsy is assumed, as well as certain possibility of anti-inflammatory and immune drugs application in anticonvulsant and antiepileptic therapy.

作者简介

N. Surina

Lomonosov Moscow State University

编辑信件的主要联系方式.
Email: Opera_ghost@inbox.ru

PhD (Biology), Senior Research Associate, Biology Department

俄罗斯联邦, Moscow

I. Fedotova

Lomonosov Moscow State University

Email: Opera_ghost@inbox.ru

PhD (Biology), Senior Research Associate, Biology Department

俄罗斯联邦, Moscow

I. Poletaeva

Lomonosov Moscow State University

Email: Opera_ghost@inbox.ru

PhD, MD (Biology), Leading Research Associate, Biology Department

俄罗斯联邦, Moscow

参考

  1. Balosso S., Ravizza T., Perego C., Peschon J., Campbell I.L., de Simoni M.G., Vezzani A. Tumor necrosis factor-alpha inhibits seizures in mice via p75 receptors. Ann. Neurol., 2005, Vol. 57, pp. 804-812.
  2. Benczik, M., Gaffen, S.L. The interleukin IL-2 family cytokines: survival and proliferation signaling pathways in T lymphocytes. Immunol. Invest., 2004, Vol. 33, pp. 109-142.
  3. de Luca G., di Giorgio R.M., Macaione S., Calpona P.R., Costantino S., di Paola E.D., de Sarro A., CilibertoG., de Sarro G. Susceptibility to audiogenic seizure and neurotransmitter amino acid levels in different brain areas of IL-6-deficient mice. Pharmacol. Biochem. Behav., 2004, Vol. 78, pp. 75-81.
  4. de Souza Bernardino T.C., Teixeira A.L., Miranda A.S., Guidine P.M., Rezende G., Doretto M.C., Castro G.P., Drummond L., Dutra Moraes M.F., Lopes Tito P.A., Pinheiro de Oliveira A.C., Reis H.J. Wistar Audiogenic Rats (WAR) exhibit altered levels of cytokines and brain derived neurotrophic factor following audiogenic seizures. Neurosci. Lett., 2015, Vol. 597, pp. 154-158.
  5. Garcia-Cairasco N., Umeoka E.H.L., Cortes de Oliveira J.A. The Wistar Audiogenic Rat (WAR) strain and its contributions to epileptology and related comorbidities: History and perspectives. Epilepsy Behav., 2017, Vol. 71, pp. 250-273.
  6. Fedotova I.B., Surina N.M., Nikolaev G.M., Poletaeva I.I. Subthreshold corazol doses induced generalized seizures in audigenic seizure-prone rats. Intern. J. Neurol. Brain Disord., 2016, Vol. 3, pp. 1-6.
  7. Ichiyama T., Suenaga N., Kajimoto M., Tohyama J., Isumi H., Kubota M., Mori M., Furukawa S. Serum and CSF levels of cytokines in acute encephalopathy following prolonged febrile seizures. Brain. Dev., 2008, Vol. 30, no. 1, pp.47-52.
  8. Lehtimaki K.A., Keränen T., Palmio J., Mäkinen R., Hurme M., Honkaniemi J., Peltola J. Increased plasma levels of cytokines after seizures in localization-related epilepsy. Acta Neurol. Scand., 2007, Vol. 116, no. 4, pp. 226-230.
  9. Onat F. Astrocytes and absence epilepsy. Br. J. Pharmacol., 2013, Vol. 168, no. 5, pp. 1086-1087.
  10. Peltola J., Palmio J., Korhonen L., Suhonen J., Miettinen A., Hurme M., Lindholm D., Keranen T. Interleukin-6 and Interleukin-1 receptor antagonist in cerebrospinal fluid from patients with recent tonic-clonic seizures. Epilepsy Res., 2000, Vol. 41, pp. 205-211.
  11. Poletaeva I.I., Surina N.M., Kostina Z.A., Perepelkina O.V., Fedotova I.B. The Krushinsky-Molodkina rat strain: The study of audiogenic epilepsy for 65 years. Review Article Epilepsy Behav., 2017, Vol. 71, Pt B, pp. 130-141.
  12. Ramos A.B., Cruz R.A., Villemarette-Pittman N.R., Olejniczak P.W., Mader J.E.C (2019) Dexamethasone as Abortive Treatment for Refractory Seizures or Status Epilepticus in the Inpatient Setting. J. Investig. Med. High Impact Case Rep., 2019, Vol. 7, 2324709619848816. doi: 10.1177/2324709619848816.
  13. Sayyah M., Beheshti S., Shokrgozar M.A., Eslami-far A., Deljoo Z., Khabiri A.R., Rohani A.H. Antiepileptogenic and anticonvulsant activity of interleukin-1 beta in amygdala-kindled rats. Exp. Neurol., 2005, Vol. 191, no. 1, pp. 145-153.
  14. Surina N.M., Fedotova I.B., Poletaeva I.I. The Effects of acute and chronic infusions of dexamethasone on audiogenic seizures and catalepsy in rats of krushinsky–molodkina and “0” strains. J. Evol. Biochem. Physiol., 2022, Vol. 58, pp. 1110-1118.
  15. Vezzani A., Balosso S., Aronica E., Ravizza T. Basic mechanisms of status epilepticus due to infection and inflammation. Epilepsia, 2009, Vol. 50, Suppl. 12, pp. 56-57.

补充文件

附件文件
动作
1. JATS XML
2. Figure 1. IL-1 concentrations in the brain tissues of the KM and “0” strain rats: A, dorsal striatum; B, brain stem Note. Cytokine concentrations in pg/ml are presented as Me (Q0.25-Q0.75). Background state (white columns) and 4 hours after sound exposure (gray columns). *, **, significant difference, p < 0.05 and 0.01, respectively.

下载 (156KB)
3. Figure 2. Dorsal striatum IL-2 1 I (A) and IL-6 (B) concentrations in rats of KM and “0” strain Note. As for Figure 1.

下载 (164KB)
4. Figure 3. Dorsal striatum (A) and brain stem (B) TNF concentrations in rats of KM and “0” strain Note. As for Figure 1.

下载 (127KB)

版权所有 © Сурина Н., Федотова И., Полетаева И., 2024

Creative Commons License
此作品已接受知识共享署名 4.0国际许可协议的许可

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).