anatomyЖурнал анатомии и гистопатологииJournal of Anatomy and Histopathology2225-7357N.N. Burdenko Voronezh State Medical University10.18499/2225-7357-2020-9-3-72-85anatomy-1160Research ArticleОБЗОРНЫЕ СТАТЬИREVIEW ARTICLESМолекулярные и клеточные механизмы повреждения центральной нервной системы при COVID-19Molecular and cellular mechanisms of central nervous system alteration in COVID-19АлексееваН. Т.AlexeevaN. T.

Воронеж

Voronezh

СоколовД. А.SokolovD. A.

ул. Студенческая, 10, Воронеж, 394036, Российская Федерация

ul. Studencheskaya, 10, Voronezh, 394036, Russian Federation

janhist@yandex.ruНикитюкД. Б.NikityukD. B.

Москва

Moscow

КлочковаС. В.KlochkovaS. V.

Москва

Moscow

КварацхелияА. Г.KvaratskheliyaA. G.

Воронеж

Voronezh

ФГБОУ ВО «Воронежский государственный медицинский университет им. Н.Н. Бурденко» Минздрава РоссииРоссияN.N. Burdenko Voronezh State Medical UniversityRussian FederationВоронежский государственный медицинский университет им. Н.Н. БурденкоРоссияN.N. Burdenko Voronezh State Medical UniversityRussian FederationФГБУН «Федеральный исследовательский центр питания, биотехнологии и безопасности пищи»; ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)РоссияThe Federal Research Centre of Biotechnology and Food Safety; I.M. Sechenov First Moscow State Medical University (Sechenov University)Russian FederationФГАОУ ВО «Российский университет дружбы народов»; ГАУЗ «Московский научно-практический центр медицинской реабилитации, восстановительной и спортивной медицины ДЗМ»РоссияPeoples Friendship University of Russia (RUDN University); Moscow Scientific and Practical Center for Medical Rehabilitation, Rehabilitation and Sports MedicineRussian Federation202010102020937285Copyright © Алексеева Н.Т., Соколов Д.А., Никитюк Д.Б., Клочкова С.В., Кварацхелия А.Г., 20202020Алексеева Н.Т., Соколов Д.А., Никитюк Д.Б., Клочкова С.В., Кварацхелия А.Г.Alexeeva N.T., Sokolov D.A., Nikityuk D.B., Klochkova S.V., Kvaratskheliya A.G.This work is licensed under a Creative Commons Attribution 4.0 License.https://anatomy.elpub.ru/jour/article/view/1160

Продолжающаяся пандемия коронавирусной болезни – 2019 (COVID-19) диктует необходимость изучения молекулярных и клеточных механизмов взаимодействия возбудителя и организма человека. Проявление неврологических симптомов у некоторых пациентов с COVID-19 представляет проблему для нейробиологов в виду недостаточно изученного патоморфогенеза заболевания. В настоящем обзоре систематизированы литературные данные, отражающие пути проникновения SARS-CoV-2 в головной мозг, особенности его взаимодействия с нейронами, нейроглией и иммунными клетками. Показано, что основными механизмами нейроинвазии SARS-CoV-2 предположительно являются ретроградный аксональный транспорт по волокнам обонятельного и блуждающего нервов; проникновение через поврежденный гематоэнцефалический барьер (ГЭБ) или миграция иммунокомпетентных клеток, содержащих вирусные частицы, через неповрежденный ГЭБ. Установлено, что вирус-индуцибельная гибель нейронов обусловлена не только прямым цитотоксическим эффектом, но также обусловлена дисрегуляцией ренинангиотензиновой системы мозга и высвобождением большого количества воспалительных цитокинов как проявлением «цитокинового шторма». Продемонстрировано участие клеток нейроглии в инициации и поддержании нейровоспалительных и нейродегенеративных процессов вследствие активации их провоспалительного фенотипа. Обсуждается роль тучных клеток вмеханизмах противовирусной защиты и воспалительных реакциях.

The ongoing coronavirus disease 2019 (COVID-19) pandemic dictates the need to study the molecular and cellular mechanisms of interaction between the pathogen and the human body. The manifestation of neurological symptoms in some patients with COVID-19 is a problem for neuroscientists due to the insufficiently understood pathomorphogenesis of the disease. This review systematizes the literature data reflecting the ways of penetration of SARS-CoV-2 into the brain, features of its interaction with neurons, neuroglia, and immune cells. It has been shown that the main mechanisms of SARS-CoV-2 neuroinvasion are presumably retrograde axonal transport along the fibers of the olfactory and vagus nerves; penetration through the damaged blood-brain barrier (BBB) or migration of immunocompetent cells containing viral particles through the intact BBB. It was found that virusinducible neuronal death is caused not only by a direct cytotoxic effect, but also due to dysregulation of the reninangiotensin system of the brain and the release of a large amount of inflammatory cytokines as a manifestation of a “cytokine storm”. The participation of neuroglial cells in the initiation and maintenance of neuroinflammatory and neurodegenerative processes due to the activation of their proinflammatory phenotype has been demonstrated. The role of mast cells in antiviral defense mechanisms and inflammatory reactions is discussed.

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The authors declare that there are no conflicts of interest present.