Preview

Neurology, Neuropsychiatry, Psychosomatics

Advanced search

The role of neuroinflammation in the pathogenesis of epilepsy

https://doi.org/10.14412/2074-2711-2018-1S-38-45

Full Text:

Abstract

Over the past decade, there has been a large amount of evidence indicating neuroendocrine, biochemical, and immune disorders in many acute and chronic central nervous system (CNS) diseases,  including epilepsy, which made the authors consider the  inflammatory theory of epileptogenesis. The chronic inflammatory  process in epilepsy is believed to be facilitated by the activation of  microglia and astrogliosis, which are accompanied by neuronal  damage. The main postulate of this type of investigation is the  assumption that the basis for CNS inflammation is blood-brain barrier (BBB) damage. Cytokines are presumed to play the  greatest role in this process, mainly because they are natural pro-  and anticonvulsants.

Patients and methods. Examinations were made in 160 patients with epilepsy (drug-resistant epilepsy (n = 80) and controlled epilepsy (n = 80)) and 30 apparently healthy donors. The blood and  cerebrospinal fluid (CSF) levels of the cytokines interleukin (IL)-1β,  IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), IL-1 receptor  antagonist (IL-1RA), soluble IL-2 receptor (sIL-2R), brain- derived neurotrophic factor (BDNF), S100b protein, С-reactive  protein (CRP), and albumins were analyzed using a solid-phase  enzyme-linked immunoabsorbent assay. Statistical analysis was performed using Student’s t-test and Mann-Whitney U-test.  Differences at p <0.05 were regarded as statistically significant.

Results and discussion. The investigation showed that the patients with epilepsy had a substantially impaired plasma cytokine profile: higher levels of proinflammatory cytokines, such as Il-1β, IL-8, and  TNF, and a lower concentration of IL-1 RA. The elevated CSF levels of the cytokines Il-1β and IL8 in patients with epilepsy suggest that  BBB is impaired and a systemic inflammatory process exists while  the absence of IL-1RA indicates that protective inflammation factors  in blood and CSF are reduced.

About the Authors

L. V. Lipatova
V.M. Bekhterev National Medical Research Center of Psychiatry and Neurology, Ministry of Health of Russia
Russian Federation
3, Bekhterev St., Saint Petersburg 192019


N. B. Serebryanaya
I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia
Russian Federation
41, Kirochnaya St., Saint Petersburg 191015


N. A. Sivakova
V.M. Bekhterev National Medical Research Center of Psychiatry and Neurology, Ministry of Health of Russia
Russian Federation
3, Bekhterev St., Saint Petersburg 192019


References

1. Scheffer IE, French J, Hirsch E, et al. Classification of the epilepsies: New concepts for discussion and debate – Special report of the ILAE Classification Task Force of the Commission for Classification and Terminology. Epilepsia Open. 2016;1(1-2):37-44. doi: 10.1002/epi4.5

2. Корнева ЕА, Шанин СН, Рыбакина ЕГ. Интерлейкин-1 в реализации стресс-индуцированных изменений функций иммунной системы. Российский физиологический журнал им. И.М. Сеченова. 2000;86(3):292- 302 [Korneva EA, Shanin SN, Rybakina EG. Interleukin-1 in the implementation of stressinduced changes in the functions of the immune system. Rossijskij Fiziologicheskij Zhurnal im. I.M. Sechenova. 2000;86(3):292- 302 (In Russ.)].

3. Aarli JA, Fontana A. Immunological aspects of epilepsy. Epilepsia. 1980;21(5):451-7.

4. Leubowitz S, Hughes RAC. Immunology of the nervous system. In: Current topics in immunology. Vol. 17. London: Edward Arnold; 1983. 304 p.

5. Сепиашвили РИ. Основы физиологии иммунной системы. Москва: Медицина-Здоровье; 2003. 240 c. [Sepiashvili RI. Osnovy fiziologii immunnoy sistemy [Fundamentals of the Physiology of the Immune System]. Moscow: Medicina-Zdorov'e; 2003. 240 p. (In Russ.)].

6. Vezzani A, Moneta D, Richichi C, et al. Functional role of inflammatory cytokines and antiinflammatory molecules in seizures and epileptogenesis. Epilepsia. 2002;43 Suppl. 5:30-5. doi: 10.1046/j.1528-1157.43.s.5.14.x

7. Lehtimä ki KA, Kerä nen T, Huhtala H, et al. Regulation of IL6 system in cerebrospinal fluid and serum compartments by seizures: the effect of seizure type and duration. J Neuroimmunol. 2004;152(1):121-5. doi: 10.1016/j.jneuroim.2004.01.024

8. Мазо ГЭ, Дубинина ЕЕ, Крижановский АС. Воспаление и депрессия: роль окислительного стресса, гормональных и клеточных факторов. Журнал неврологии и психиатрии им. С.С. Корсакова. 2014;(1):80-4 [Mazo GE, Dubinina EE, Krizhanovskij AS. Inflammation and depression: the role of oxidative stress, hormonal and cellular factors. Zhurnal Nevrologii i Psihiatrii im. S.S. Korsakova. 2014;(1):80-4 (In Russ.)].

9. Гуляева НВ. Коннектопатии, пластичность, системы цитокинов и нейротрофических факторов: механизмы коморбидности неврологических и психических заболеваний и перспективы фармакотерапии. В кн.: Гусев ЕИ, Гехт АБ, редакторы. Болезни – медицинские и социальные аспекты. Москва: ООО «Буки-Веди»; 2016. С. 733-43 [Guljaeva NV. Connepopathy, plasticity, cytokine system and neurotrophic factors: mechanisms of comorbidity of neurological and mental diseases and prospects of pharmacotherapy. In: Gusev EI, Geht AB, editors. Bolezni – meditsinskie i sotsial'nye aspekty [Diseases – medical and social aspects]. Moscow: OOO «Buki-Vedi»; 2016. P. 733-43 (In Russ.)].

10. Ruiz-Gimenez J, Sanchez-Alvarezb JC, Canadillas-Hidalgoc F, Serrano-Castrod PJ; on behalf of the Andalusian Epilepsy Society. Antiepileptic treatment in patients with epilepsy and other comorbidities. Seizure. 2010;19:375- 82. doi: 10.1016/j.seizure.2010.05.008

11. Maes M, Galecki P, Chang YS, et al. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Progr Neuro-Psychopharmacol Biol Psychiatry. 2011;35(3):676-92. doi: 10.1016/j.pnpbp.2010.05.004

12. De Simoni MG, Perego C, Ravizza T, et al. Inflammatory cytokines and related genes are induced in the rat hippocampus by limbic status epilepticus. Eur J Neurosci. 2000;12(7):2623-33. doi: 10.1046/j.1460-9568.2000.00140.x

13. Oby E, Janigro D. The blood-brain barrier and epilepsy. Epilepsia. 2006;47(11):1761-74. doi: 10.1111/j.1528-1167.2006.00817.x

14. Van Vliet EA, da Costa Araujo S, Redeker S, et al. Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy. Brain. 2007;130(2):521-34. doi: 10.1093/brain/awl318

15. Juhasz G, Erdi B, Sass M, Neufeld TP. Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes Development. 2007;21(23):3061-6. doi: 10.1101/gad.1600707

16. Marchi N, Fan Q, Ghosh C, et al. Antagonism of peripheral inflammation reduces the severity of status epilepticus. Neurobiol Dis. 2009;33(2):171-81. doi: 10.1016/j.nbd.2008.10.002

17. Vezzani A, Moneta D, Richichi C, et al. Functional role of proinflammatory and antiinflammatory cytokines in seizures. Adv Exp Med Biol. 2004;548:123-33. doi: 10.1007/978-1-4757-6376-8_10

18. Vezzani A, Balosso S, Ravizza T. The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun. 2008;22(6):797-803. doi: 10.1016/j.bbi.2008.03.009

19. Diamond ML, Ritter AC, Failla MD, et al. IL1b associations with posttraumatic epilepsy development: A genetics and biomarker cohort study. Epilepsia. 2014;55(7):1109-19. doi: 10.1111/epi.12628

20. Кетлинский СА, Симбирцев АС. Цитокины. Санкт-Петербург: Фолиант; 2008. 552 с. [Ketlinskij SA, Simbircev AS. Tsitokiny [Cytokines]. St. Petersburg: Foliant; 2008. 552 p. (In Russ.)].

21. Симбирцев АС. Интерлейкин-1. Физиология. Патология. Клиника. Санкт-Петербург: Фолиант; 2011 [Simbirtsev AS. Interleykin-1. Fiziologiya. Patologiya. Klinika [Interleukin-1. Physiology. Pathology. Clinic]. St. Petersburg: Foliant; 2011. (In Russ.)].

22. Samland H, Huitron-Resendiz S, Masliah E, et al. Profound increase in sensitivity to glutamatergic but not cholinergic agonist induced seizures in transgenic mice with astrocyte production of IL 6. J Neurosci Res. 2003;73(2):176-87. doi: 10.1002/jnr.10635

23. Yuhas Y, Weizman A, Ashkenazi S. Bidirectional concentration-dependent effects of tumor necrosis factor alpha in Shigella dysenteriae-related seizures. Infect Immun. 2003;71(4):2288-91. doi: 10.1128/iai.71.4.2288-2291.2003

24. Lehrner J, Kalchmayr R, Serles W, et al. Health-related quality of life (HRQOL), activity of daily living (ADL) and depressive mood disorder in temporal lobe epilepsy patients. Seizure. 1999;8(2):88-92. doi: 10.1053/seiz.1999.0272

25. Kobau R, Gilliam F, Thurman DJ. Prevalence of self-reported epilepsy or seizure disorder and its associations with self-reported depression and anxiety: results from the 2004 Health Styles Survey. Epilepsia. 2006;47:1915- 21. doi: 10.1111/j.1528-1167.2006.00612.x

26. Тиганов АС. Эпилепсия. В кн.: Тиганов АС, редактор. Руководство по психиатрии: В 2-х томах. Москва: Медицина; 1999. Т. 2. С. 12-56. [Tiganov AS. Epilepsy. In: Tiganov AS, editor. Rukovodstvo po psihiatrii [Manual of Psychiatry]. Moscow: Medicina; 1999. Vol. 2. P. 12-56 (In Russ.)].

27. Maes M, Bosmans E, Meltzer HY, et al. Interleukin-1 beta: a putative mediator of HPA axis hyperactivity in major depression? Am J Psychiatry. 1993a;150(8):1189-93. doi: 10.1176/ajp.150.8.1189

28. Maes M, Scharpe S, Meltzer HY, et al. Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic- pituitary-adrenal axis in severe depression. Psychiatr Res. 1993b;49(1):11-27. doi: 10.1016/0165-1781(93)90027-e

29. Song CX, Szulwach E, Fu Y, et al. Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nat Biotechnol. 2011;29(1):68-72. doi: 10.1038/nbt.1732

30. Leonard B, Maes M. Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev. 2012;36(2):764-85. doi: 10.1016/j.neubiorev.2011.12.005

31. Zou JY, Crews FT. TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition. Brain Res. 2005;1034(1-2):11-24. doi: 10.1016/j.brainres.2004.11.014

32. Wahab A. Difficulties of treatment and management of epilepsy and challenges of new drug development. Pharmaceuticals. 2010;3:2090-110. doi: 10.3390/ph3072090

33. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy. Epilepsia. 2010;51(6):1069-77. doi: 10.1111/j.1528-1167.2009.02397.x

34. Гусев ЕИ, Гехт АБ. Эпилепсия и дизрегуляционная система. В кн.: Гусев ЕИ, Крыжановский ГН, редакторы. Дизрегуляционная патология нервной системы. Москва: Медицинское информационное агентство; 2009. С. 196-214 [Gusev EI, Geht AB. Epilepsy and dysregulation system In: Gusev EI, Kryzhanovskiy GN. Dizreguljacionnaja patologija nervnoj sistemy [Disinfection pathology of the nervous system]. Moscow: Meditsinskoe informatsionnoe agentstvo; 2009. P. 196-214. (In Russ.)].

35. Ettinger A, Reed M, Cramer J. Depression and comorbidity in community-based patients with epilepsy or asthma. Neurology. 2004;63:1008-14. doi: 10.1212/01.wnl.0000138430.11829.61

36. Болдырев АИ. Эпилепсия у взрослых. Москва: Медицина; 1971. 368 с. [Boldyrev AI. Epilepsiya u vzroslykh [Epilepsy in adults]. Moscow: Medicina; 1971. 368 p. (In Russ.)].

37. Карлов ВА. Эпилепсия у детей и взрослых женщин и мужчин: Руководство для врачей. Москва: Медицина; 2010. 720 с. [Karlov VA. Epilepsiya u detey i vzroslykh zhenshchin i muzhchin: Rukovodstvo dlya vrachey [Epilepsy in children and adult women and men: A Guide for Physicians]. Moscow: Medicina; 2010. 720 p. (In Russ.)].

38. Vezzani A, Moneta D, Conti M, et al. Powerful anticonvulsant action of ИЛ1 receptor antagonist on intracerebral injection and astrocytic overexpression in mice. Proc Nat Acad Sci. 2000;97(21):11534-9. doi: 10.1073/pnas.190206797

39. Blumer D, Montouris G, Davies K. The interictal dysphoric disorder: recognition, pathogenesis, and treatment of the major psychiatric disorder of epilepsy. Epilepsy Behav. 2004;5:826-40. doi: 10.1016/j.yebeh.2004.08.003

40. Егорова ВН, Попович АМ, Бабаченко ИВ и др. Интерлейкин-2: обобщенный опыт клинического применения. Санкт-Петербург: Ультра Принт; 2012. 98 с. [Egorova VN, Popovich AM, Babachenko IV, et al. Interleykin-2: obobshchennyy opyt klinicheskogo primeneniya [Interleukin-2: generalized clinical experience]. St. Petersburg: Ul'tra Print; 2012. 98 p. (In Russ.)].

41. Cardona AE, Li M, Liu L, et al. Chemokines in and out of the central nervous system: much more than chemotaxis and inflammation. J Leuk Biol. 2008;84(3):587-94. doi: 10.1189/jlb.1107763

42. Huang Z, Dauer DJ, Ha GK, et al. Interleukin-2 deficiency-induced T cell autoimmunity in the mouse brain. Neurosci Lett. 2009;463(1):44-8. doi: 10.1016/j.neulet.2009.07.013

43. Sapolsky RM. Is impaired neurogenesis relevant to the affective symptoms of depression? Biol Psychiatr. 2004;56(3):137-9. doi: 10.1016/j.biopsych.2004.04.012

44. Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev. 2012;64(2):238-58. doi: 10.1124/pr.111.005108

45. LaFrance WC Jr, Leaver K, Stopa EG, et al. Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures. Neurology. 2010;75(14):1285-91. doi: 10.1212/wnl.0b013e31820e44fb

46. Isackson PJ, Huntsman MM, Murray KD, Gall CM. BDNF mRNA expression is increased in adult rat forebrain after limbic seizures: temporal patterns of induction distinct from NGF. Neuron. 1991;6:937-48. doi: 10.1016/0896-6273(91)90234-q

47. Binder DK, Routbort MJ, McNamara JO. Immunohistochemical evidence of seizureinduced activation of trk receptors in the mossy fiber pathway of adult rat hippocampus. Neurosci. 1999;19:4616-26. doi: 10.1523/JNEUROSCI.19-11-04616.1999

48. Dombrowsky SM, Desai SV, Marrini M, et al. Overtreatment of multidrug resistance genes in endothelial cells from patients of refractory epilepsy. Epilepsia. 2001;42:1501-6. doi: 10.1046/j.1528-1157.2001.12301.x

49. McNamura JO, He XP, Kotloski R. How to prevent the development of spontaneous recurrent seizures? The neurotrophin receptor TrKb is required for epileptogenesis in the kindling model. Epilepsy Res. 2006;69:216-9.

50. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Ann Rev Neurosci. 2001;24:677. doi: 10.1146/annurev.neuro.24.1.677

51. Иванова СА, Федоренко ОЮ, Смирнов ЛП, Семке АВ. Поиск биомаркеров и разработка фармакогенетических подходов к персонализированной терапии больных шизофренией. Сибирский вестник психиатрии и наркологии. 2013;(1):12-6 [Ivanova SA, Fedorenko OYu, Smirnov LP, Semke AV. Search for biomarkers and development of pharmacogenetic approaches to personalized therapy of patients with schizophrenia. Sibirskij Vestnik Psihiatrii i Narkologii. 2013;(1):12-6 (In Russ.)].

52. Costigliola V, Gahan P, Golubnitschaja O. Predictive medicine as the new philosophy in health care. In: Golubnitschaja O, editor. Predictive Diagnostics and Personalized Treatment: Dream or Reality. New York: Nova Science Publishers; 2009. P. 1-3.

53. Jain KK. Role of nanobiotechnology in the development of personalized medicine. Nanomed. 2009;4:249-52. doi: 10.1159/000319928

54. Vezzani A, Granata T. Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia. 2005;46(11):1724-43. doi: 10.1111/j.1528-1167.2005.00298.x

55. Librizzi L, Ravizza T, Vezzani A, de Curtis M. Expression of IL1 beta induced by epileptiform activity in the isolated guinea pig brain in vitro. Epilepsia. 2010;51(Suppl. 4):18.

56. Siv M. Role of Inflammation in Epilepsy and Treatment with IVIg. Wingate University School of Pharmacy, 5.17. 2010. [Электронный ресурс]. Режим доступа: http://www.iceepilepsy.org/role-of-inflammation-in-epilepsyand-treatment-with-ivig.html

57. Коляскина ГИ. Иммунология в психиатрии. В кн.: Тиганов АС, редактор. Руководство по психиатрии. В 2-х томах. Москва: Медицина; 1999. Т. 1. С. 60, 190-211 [Koljaskina GI. Immunology in Psychiatry. In: Tiganov AS, editor. Rukovodstvo po psihiatrii [Manual of Psychiatry]. Moscow: Medicina; 1999. Vol. 1. P. 190-211 (In Russ.)].

58. Ветлугина ТП, Семке ВЯ. Клиническая психонейроиммунология на современном этапе. Сибирский вестник психиатрии и наркологии. 2003;(1):34-6 [Vetlugina TP, Semke VY. Clinical psychoneuroimmunology at the present stage. Sibirskij Vestnik Psihiatrii i Narkologii. 2003;(1):34-6 (In Russ.)].

59. Коляскина ГИ, Секирина ТП, Андросова СГ и др. Иммунная система при шизофрении. Сибирский вестник психиатрии и наркологии. 2003;(1):21-4 [Koljaskina GI, Sekirina TP, Androsova SG, et al. Immune system in schizophrenia. Sibirskij Vestnik Psihiatrii i Narkologii. 2003;(1):21-4 (In Russ.)].

60. Козловская ГВ, Клюшник ТП, Калинина МА и др. Предварительные результаты применения нового иммуномодулятора ронколейкина в комплексной терапии детей, больных шизофренией. Психиатрия и психофармакотерапия. 2005;7(5):259-62 [Kozlovskaja GV, Kljushnik TP, Kalinina VA, et al. Preliminary results of application of new immunomodulator Roncoleukin in complex therapy of children with schizophrenia. Psihiatriya i Psihofarmakoterapiya. 2005;7(5):259-62 (In Russ.)].

61. Хайрулина РМ. Ронколейкин в педиатрической практике. Опыт применения, перспективы использования: методические рекомендации. Уфа; 1998. 26 с. [Hajrulina RM. Ronkoleykin v pediatricheskoy praktike. Opyt primeneniya, perspektivy ispol'zovaniya: metodicheskie rekomendatsii [Roncoleukin in pediatric practice. Experience of application, prospects of use: methodical recommendations]. Ufa, 1998. 26 p. (In Russ.)].

62. Козлов ВК. Ронколейкин, биологическая активность, иммунокорригирующая эффективность и клиническое применение. Санкт-Петербург: Изд-во СПбГУ; 2002. 84 с. [Kozlov VK. Ronkoleykin, biologicheskaya aktivnost', immunokorrigiruyushchaya effektivnost' i klinicheskoe primenenie [Roncoleukin, biological activity, immunocorrecting efficacy and clinical application]. St. Petersburg: Publishing house of SPbSU; 2002. 84 p. (In Russ.)].

63. Фисенко НС, Морозов НМ, Саядова ЗС. Возможности фармакологической коррекции Ронколейкином иммунорегуляторных взаимодействий у пациентов с ремиттирующей формой рассеянного склероза. Цитокины и воспаление. 2002;1(2):103 [Fisenko NS, Morozov NM, Sajadova ZS. Possibilities of pharmacological correction of Roncoleukin immunoregulatory interactions in patients with a remitting form of multiple sclerosis. Citokiny i Vospalenie. 2002;1(2):103 (In Russ.)].

64. Козлов ВК. Иммунопатогенез и цитокинотерапия хирургического сепсиса: пособие для врачей. Санкт-Петербург: Изд-во «Ясный Свет»; 2002. 48 с. [Kozlov VK. Immunopatogenez i tsitokinoterapiya khirurgicheskogo sepsisa: posobie dlya vrachey [Immunopathogenesis and cytokine therapy of surgical sepsis: a manual for physicians]. St. Petersburg: Ysnyi Svet; 2002. 48p. (In Russ.)].

65. Курманова ГМ, Рамазанова ШХ, Мажитова ЗХ. Опыт применения Ронколейкина у детей, больных бронхиальной астмой в приступный период. Медицинская иммунология. 2003;5(3-4):233 [Kurmanova GM, Ramazanova ShH, Mazhitova ZH. Experience in the use of Roncoleukin in children with bronchial asthma during the offensive period. Medicinskaja Immunologija. 2003;5(3-4):233 (In Russ.)].

66. Егорова ВН, Попович АМ. Ронколейкин®: результаты клинических испытаний. Санкт-Петербург: Альтернативная полиграфия; 2004. 48 с. [Egorova VN, Popovich AM. Ronkoleykin®: rezul'taty klinicheskikh ispytaniy [Roncoleukin®: results of clinical trials]. St. Petersburg: Al'ternativnaya poligrafiya; 2004. 48 p. (In Russ.)].

67. Крыжановский ГН, Гусев ЕИ, Гехт АБ. Фундаментальные механизмы и общие закономерности дизрегуляционной патологии нервной системы. В кн.: Гусев ЕИ, Крыжановский ГН, редакторы. Дизрегуляционная патология нервной системы. Москва: Медицинское информационное агентство; 2009. С. 196-214 [Kryzhanovskij GN, Gusev EI, Geht AB. Fundamental mechanisms and general patterns of disregulatory pathology of the nervous system. In: Gusev EI, Kryzhanovskiy GN, editors. Dizreguljacionnaja patologija nervnoj sistemy [Disregulatory pathology of the nervous system]. Moscow: Medical News Agency; 2009. P. 196-214 (In Russ.)].

68. Егоренкова ЕВ, Розентул АШ, Смолянинов АБ. Индивидуальные психологические особенности больных цереброваскулярной болезнью на фоне цитокиновой терапии. Нейроиммунопатология. 2003;1(2):49-50 [Egorenkova EV, Rozentul ASh, Smoljaninov AB. Individual psychological features of patients with cerebrovascular disease on the background of cytokine therapy. Nejroimmunopatologija. 2003;1(2):49-50 (In Russ.)].

69. Mahendran R, Chan YH. Interleukin-2 levels in chronic schizophrenia patients. Ann Acad Med Singapore. 2004;33(3):320-3.


For citation:


Lipatova L.V., Serebryanaya N.B., Sivakova N.A. The role of neuroinflammation in the pathogenesis of epilepsy. Neurology, Neuropsychiatry, Psychosomatics. 2018;10(1S):38-45. (In Russ.) https://doi.org/10.14412/2074-2711-2018-1S-38-45

Views: 387


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)