Ulyanovsk Medico-biological Journal

BIOLOGICAL SCIENCES

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DOI 10.34014/2227-1848-2023-3-122-130

CYTOMETRIC PARAMETERS OF CEREBRAL CORTEX NEURONS IN COVID-19

T.I. Kuznetsova, E.V. Slesareva, K.E. Nikishin, M.M. Gadzhiarslanova, A.A. Vlasova

Ulyanovsk State University, Ulyanovsk, Russia

 

COVID-19 has recently been one of the greatest challenges of public health services worldwide. SARS-CoV-19 affects not only the respiratory, but also other systems, including the brain. It causes strokes, meningitis, encephalopathy, encephalitis, etc. Due to the multifactorial nature and complexity of COVID-19 pathogenesis, studying its impact on brain tissue is relevant.

The aim of the work is to study the cytometric parameters of neurons in the parietal-occipital lobe of the cerebral cortex in patients who died due to COVID-19.

Materials and Methods. For histomorphological examination, autopsies of the parietal-occipital lobe of the cerebral cortex were fixed in 10 % neutral formalin and embedded in paraffin. Cross sections (5–6 μm) were stained with hematoxylin-eosin. Histologic specimens were studied under a light microscope. Morphometric measurements of the nucleus and cytoplasm area of neurons of the parietal-occipital lobe of the cerebral cortex were performed on the images. The nuclear-cytoplasmic ratio was calculated. The results of the histomorphological study were analyzed along with the medical history. For comparison, autopsies of the parietal-occipital lobe of the cerebral cortex from patients who died from cerebral infarction were used.

Results. Nucleus and cytoplasm areas of neurons in the pyramidal and ganglionic layers of the cerebral cortex were measured. In the cerebral cortex, COVID-19 mainly affects the microvasculature vessels, disrupting their permeability and causing hemorrhages. Damage to the neurons of the cerebral cortex is less pronounced and does not have any specific pathomorphological picture, which corresponds to the pattern of long-term ischemic effects on the gray matter.

Key words: COVID-19, neurons, morphometry, nuclear-cytoplasmic ratio.

 

Conflict of interest. The authors declare no conflict of interest.

Author contributions

Research concept and design: Slesareva E.V.

Literature search, participation in the research study, medical history and clinical analysis: Nikishin K.E.

Histological examination and morphometry: Kuznetsova T.I., Gadzhiarslanova M.M., Vlasova A.A.

Statistical data processing: Kuznetsova T.I., Gadzhiarslanova M.M., Vlasova A.A.

Data analysis and interpretation: Slesareva E.V.

Text writing and editing Kuznetsova T.I., Slesareva E.V.

 

References

  1. Statistika VOZ o novoy koronovirusnoy infektsii COVID-19 po miru [WHO Coronavirus (COVID-19) Dashboard]. Available at: https://covid19.who.int (accessed: March 29, 2023).

  2. Niraj Kumar Jha, Shreesh Ojha, Saurabh Kumar Jha, Harish Dureja, Sachin Kumar Singh, Shakti D. Shukla, Dinesh Kumar Chellappan, Gaurav Gupta, Shanu Bhardwaj, Neeraj Kumar, Madhan Jeyaraman, Rashmi Jain, Sathish Muthu, Rohan Kar, Dhruv Kumar, Vineet Kumar Goswami, Janne Ruokolainen, Kavindra Kumar Kesari, Sandeep Kumar Singh, Kamal Dua. Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations. J Mol Neurosci. 2021; 71 (11): 2192–2209.

  3. Maury A., Lyoubi A., Peiffer-Smadja N., de Broucker T., Meppiel E. Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians. Rev Neurol (Paris). 2021; 177 (1-2): 51–64.

  4. Arbour N. Neuroinvasion by human respiratory coronoviruses. J. Virol. 2000; 74 (19): 8913–8921.

  5. Baig A.M., Khaleeq A., Ali U., Syeda H. Evidance of the COVID-19 virus targeting the CNS: tissue distribution, host virus interaction, and propoused neurotropicmechanisms. ACS Chem Neurosci. 2020; 11 (7): 995–998.

  6. Yeshun Wu, Xiaolin Xu, Zijun Chen, Jiahao Duan, Kenji Hashimoto, Ling Yang, Cunming Liu, Chun Yang. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020; 87: 18–22.

  7. Gu J., Gong E., Zhang B., Zheng J., Gao Z., Zhong Y. Myltiplay organ infection and the pathogenesis of SARS. J. Exp. Med. 2005; 202 (3): 415–424.

  8. Wang R., Pan., Zhang X., Fan X., Han M., Zhao F. Epidemiological and clinical features of 125 hospitalaised patients with COVID-19 in Fuyang Anhuinavar China. J. Infect Dis. 2020; 95: 421–428.

  9. Guo J. Coronavirus disease 2019 (COVID-19) and cardiovascular disease: a viewpoint on the potential influence of angiotensin-converting enzyme ingibitors. J Am Heart Assoc. 2020; 9 (7): e016219.

  10. Brann D.H., Tsukahara T., Weinreb C., Lipovsek M., Van den Berge K., Gong B. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19 associated anosmia. SciAdv. 2020; 6 (31): 1–28.

  11. Bryce C., Grimes Z., Pujadas E. Pathophysiology of Sars-CoV-2: targeting of the endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 autopsy experience. MedRxiv. 2020. Available at: https://www.medrxiv.org/content/10.1101/2020.05.18.20099960v1 (accessed: March 29, 2023).

  12. Channappa R., Perlman S. Pathogenic human coronavirus infection: causes and consequenses of cytokine storm and immunopathology. Semin. Immunopathology. 2017; 39: 529–539.

  13. Nazari S., Azari Jafari A., Mirmoeeni S., Sadeghian S., Eghbal Heidari M., Sadeghian S., Assarzadegan F., Mahmoud Puormand S. Central nervous system manifestations in COVID-19 patients: A systematic review and meta-analysis. Brain. Behav. 2021; 11 (5): e02025. DOI: 10.1002/brb3.2025.

  14. Higaki A., Mogi M., Iwanami J., Min L.‐J., Bai H.‐Y., Shan B.‐S., Kukida M., Yamauchi T. Beneficial Effect of Mas Receptor Deficiency on Vascular Cognitive Impairment in the Presence of Angiotensin II Type 2 Receptor. J. Am. Heart. Assoc. 2018; 7 (3): e008121. DOI: 10.1161/JAHA.117.008121.

  15. Alomari S., Abou-Mrad Z., Bydon A. COVID-19 and the central nervous system. Clin. Neurol. Neurosurg. 2020; 198: 106116. DOI: 10.1016/j.clineuro.2020.106116.

  16. Liotta E.M., Batra A., Clark J.R., Shlobin N.A., Hoffman S.C., Orban Z.S., Koralnik I.J. Frequent neurologic manifestations and encephalopathy-associated morbidity in COVID-19 patients. Ann. Clin. Transl. Neurol. 2020; 7 (11): 2221–2230. DOI: 10.1002/acn3.51210.

  17. Xia H., Lazartigues E. Angiotensin-converting enzyme 2 in the brain: propeties and future directions. J Neurochem. 2008; 107 (6): 1482–1494.

  18. Zhang H., Penninger J.M., Li Y., Zhong N., Slytsky A.S. Angiotensine-converting ensyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Invastive Care Med. 2020; 46: 586–590.

  19. Erickson M.A., Rhea E.M., Knopp R.C., Banks W.A. Interactions of SARS-CoV-2 with the blood-brain barrier. Int. J. Mol. Sci. 2021; 22 (5): 2681. DOI: 10.3390/ijms22052681.

  20. Babkina A.S., Golubev A.M., Ostrova I.V., Volkov A.V., Kuzovlev A.N. Morfologicheskie izmeneniya golovnogo mozga pri COVID-19 [Brain morphological changes in COVID-19]. Obshchaya reanimatologiya. 2021; 3. Available at: https://cyberleninka.ru/article/n/morfologicheskie-izmeneniya-golovnogo-mozga-pri-covid-19 (accessed: March 29, 2023) (in Russian).

 

Received April 12, 2023; accepted May 26, 2023.

 

Information about the authors

Kuznetsova Tat'yana Ivanovna, Candidate of Sciences (Biology), Associate Professor, Chair of Morphology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0909-734X

Slesareva Elena Vasil'evna, Doctor of Sciences (Medicine), Associate Professor, Head of the Chair of General and Clinical Morphology, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-3159-9146

Nikishin Kirill Evgen'evich, Resident, Department of Postgraduate and Pharmaceutical Education, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0125-323X

Gadzhiarslanova Malikat Magomedalievna, Medical Student, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0005-0036-3287

Vlasova Alina Alekseevna, Medical Student, Ulyanovsk State University. 432017, Russia, Ulyanovsk, L. Tolstoy St., 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0006-0298-5431

 

For citation

Kuznetsova T.I., Slesareva E.V., Nikishin K.E., Gadzhiarslanova M.M., Vlasova A.A. Tsitometricheskie parametry neyronov kory bol'shikh polushariy golovnogo mozga pri COVID-19 [Cytometric parameters of cerebral cortex neurons in COVID-19]. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2023; 3: 122–130. DOI: 10.34014/2227-1848-2023-3-122-130 (in Russian).

 

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УДК 616.91+616-091.8

DOI 10.34014/2227-1848-2023-3-122-130

ЦИТОМЕТРИЧЕСКИЕ ПАРАМЕТРЫ НЕЙРОНОВ КОРЫ БОЛЬШИХ ПОЛУШАРИЙ ГОЛОВНОГО МОЗГА ПРИ COVID-19

Т.И. Кузнецова, Е.В. Слесарева, К.Е. Никишин, М.М. Гаджиарсланова, А.А. Власова

ФГБОУ ВО «Ульяновский государственный университет», г. Ульяновск, Россия

Новая коронавирусная инфекция COVID-19 еще совсем недавно была одной из основных проблем мирового здравоохранения. Вирус SARS-CoV-19 поражает не только дыхательную, но и другие системы органов, в т.ч. и головной мозг, вызывая инсульты, менингиты, энцефалопатии, энцефалиты и пр. Из-за многофакторности и сложности патогенеза данного заболевания изучение воздействия COVID-19 на ткани головного мозга представляется весьма актуальным.

Цель работы – изучение цитометрических показателей нейронов теменно-затылочной области коры головного мозга больных, умерших от COVID-19.

Материалы и методы. Для гистоморфологического исследования аутоптаты теменно-затылочной области коры головного мозга фиксировали в 10 % нейтральном формалине и заливались в парафин. Срезы (5–6 мкм) окрашивали гематоксилин-эозином, после чего изучали гистологические препараты с помощью светового микроскопа. На снимках проводили морфометрические измерения площади ядра и цитоплазмы нейронов теменно-затылочной области коры больших полушарий, вычисляли ядерно-цитоплазматическое отношение. Результаты гистоморфологического исследования анализировали совместно с материалами истории болезни. Для сравнения использовали аутоптаты теменно-затылочной области коры больших полушарий умерших от ишемического инфаркта головного мозга.

Результаты. Были измерены площади ядра и цитоплазмы нейронов пирамидного и ганглионарного слоев коры больших полушарий. COVID-19 в коре больших полушарий преимущественно воздействует на сосуды микроциркуляторного русла, вызывая нарушение их проницаемости и развитие геморрагий. Поражение нейронов коры больших полушарий менее выражено и не имеет какой-либо специфической патоморфологической картины, что соответствует картине длительного ишемического воздействия на серое вещество головного мозга.

Ключевые слова: новая коронавирусная инфекция COVID-19, нейроны, морфометрия, ядерно-цитоплазматическое отношение.

 

Конфликт интересов. Авторы заявляют об отсутствии конфликта интересов.

Вклад авторов

Концепция и дизайн исследования: Слесарева Е.В.

Литературный поиск, участие в исследовании, работа с историями болезней, клинический анализ: Никишин К.Е.

Гистологическое исследование и морфометрия: Кузнецова Т.И., Гаджиарсланова М.М., Власова А.А.

Статистическая обработка данных: Кузнецова Т.И., Гаджиарсланова М.М., Власова А.А.

Анализ и интерпретация данных: Слесарева Е.В.

Написание и редактирование текста: Кузнецова Т.И., Слесарева Е.В.

 

Литература

  1. Статистика ВОЗ о новой коронавирусной инфекции COVID-19 по миру. URL: https://covid19.who.int (дата обращения: 29.03.2023).

  2. Niraj Kumar Jha, Shreesh Ojha, Saurabh Kumar Jha, Harish Dureja, Sachin Kumar Singh, Shakti D. Shukla, Dinesh Kumar Chellappan, Gaurav Gupta, Shanu Bhardwaj, Neeraj Kumar, Madhan Jeyaraman, Rashmi Jain, Sathish Muthu, Rohan Kar, Dhruv Kumar, Vineet Kumar Goswami, Janne Ruokolainen, Kavindra Kumar Kesari, Sandeep Kumar Singh, Kamal Dua. Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations. J Mol Neurosci. 2021; 71 (11): 2192–2209.

  3. Maury A., Lyoubi A., Peiffer-Smadja N., de Broucker T., Meppiel E. Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians. Rev Neurol (Paris). 2021; 177 (1-2): 51–64.

  4. Arbour N. Neuroinvasion by human respiratory coronoviruses. J. Virol. 2000; 74 (19): 8913–8921.

  5. Baig A.M., Khaleeq A., Ali U., Syeda H. Evidance of the COVID-19 virus targeting the CNS: tissue distribution, host virus interaction, and propoused neurotropicmechanisms. ACS Chem Neurosci. 2020; 11 (7): 995–998.

  6. Yeshun Wu, Xiaolin Xu, Zijun Chen, Jiahao Duan, Kenji Hashimoto, Ling Yang, Cunming Liu, Chun Yang. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020; 87: 18–22.

  7. Gu J., Gong E., Zhang B., Zheng J., Gao Z., Zhong Y. Myltiplay organ infection and the pathogenesis of SARS. J. Exp. Med. 2005; 202 (3): 415–424.

  8. Wang R., Pan., Zhang X., Fan X., Han M., Zhao F. Epidemiological and clinical features of 125 hospitalaised patients with COVID-19 in Fuyang Anhuinavar China. J. Infect Dis. 2020; 95: 421–428.

  9. Guo J. Coronavirus disease 2019 (COVID-19) and cardiovascular disease: a viewpoint on the potential influence of angiotensin-converting enzyme ingibitors. J Am Heart Assoc. 2020; 9 (7): e016219.

  10. Brann D.H., Tsukahara T., Weinreb C., Lipovsek M., Van den Berge K., Gong B. Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19 associated anosmia. SciAdv. 2020; 6 (31): 1–28.

  11. Bryce C., Grimes Z., Pujadas E. Pathophysiology of Sars-CoV-2: targeting of the endothelial cells renders a complex disease with thrombotic microangiopathy and aberrant immune response. The Mount Sinai COVID-19 autopsy experience. MedRxiv. 2020. URL: https://www.medrxiv.org/content/10.1101/2020.05.18.20099960v1 (дата обращения: 29.03.2023).

  12. Channappa R., Perlman S. Pathogenic human coronavirus infection: causes and consequenses of cytokine storm and immunopathology. Semin. Immunopathology. 2017; 39: 529–539.

  13. Nazari S., Azari Jafari A., Mirmoeeni S., Sadeghian S., Eghbal Heidari M., Sadeghian S., Assarzadegan F., Mahmoud Puormand S. Central nervous system manifestations in COVID-19 patients: A systematic review and meta-analysis. Brain. Behav. 2021; 11 (5): e02025. DOI: 10.1002/brb3.2025.

  14. Higaki A., Mogi M., Iwanami J., Min L.‐J., Bai H.‐Y., Shan B.‐S., Kukida M., Yamauchi T. Beneficial Effect of Mas Receptor Deficiency on Vascular Cognitive Impairment in the Presence of Angiotensin II Type 2 Receptor. J. Am. Heart. Assoc. 2018; 7 (3): e008121. DOI: 10.1161/JAHA.117.008121.

  15. Alomari S., Abou-Mrad Z., Bydon A. COVID-19 and the central nervous system. Clin. Neurol. Neurosurg. 2020; 198: 106116. DOI: 10.1016/j.clineuro.2020.106116.

  16. Liotta E.M., Batra A., Clark J.R., Shlobin N.A., Hoffman S.C., Orban Z.S., Koralnik I.J. Frequent neurologic manifestations and encephalopathy-associated morbidity in COVID-19 patients. Ann. Clin. Transl. Neurol. 2020; 7 (11): 2221–2230. DOI: 10.1002/acn3.51210.

  17. Xia H., Lazartigues E. Angiotensin-converting enzyme 2 in the brain: propeties and future directions. J Neurochem. 2008; 107 (6): 1482–1494.

  18. Zhang H., Penninger J.M., Li Y., Zhong N., Slytsky A.S. Angiotensine-converting ensyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Invastive Care Med. 2020; 46: 586–590.

  19. Erickson M.A., Rhea E.M., Knopp R.C., Banks W.A. Interactions of SARS-CoV-2 with the blood-brain barrier. Int. J. Mol. Sci. 2021; 22 (5): 2681. DOI: 10.3390/ijms22052681.

  20. Бабкина А.С., Голубев А.М., Острова И.В., Волков А.В., Кузовлев А.Н. Морфологические изменения головного мозга при COVID-19. Общая реаниматология. 2021; 3. URL: https://cyberleninka.ru/article/n/morfologicheskie-izmeneniya-golovnogo-mozga-pri-covid-19 (дата обращения: 29.03.2023).

 

Поступила в редакцию 12.04.2023; принята 26.05.2023.

 

Авторский коллектив

Кузнецова Татьяна Ивановна – кандидат биологических наук, доцент кафедры морфологии ИМЭиФК, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0909-734X

Слесарева Елена Васильевна – доктор медицинских наук, доцент, заведующий кафедрой общей и клинической морфологии ИМЭиФК, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0002-3159-9146

Никишин Кирилл Евгеньевич – ординатор факультета последипломного и фармацевтического образования, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0000-0003-0125-323X

Гаджиарсланова Маликат Магомедалиевна – студентка медицинского факультета, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0005-0036-3287

Власова Алина Алексеевна – студентка медицинского факультета, ФГБОУ ВО «Ульяновский государственный университет». 432017, Россия, г. Ульяновск, ул. Л. Толстого, 42; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it., ORCID ID: https://orcid.org/0009-0006-0298-5431

 

Образец цитирования

Кузнецова Т.И., Слесарева Е.В., Никишин К.Е., Гаджиарсланова М.М., Власова А.А. Цитометрические параметры нейронов коры больших полушарий головного мозга при COVID-19. Ульяновский медико-биологический журнал. 2023; 3: 122–130. DOI: 10.34014/2227-1848-2023-3-122-130.