THE DYNAMICS OF BIOMARKERS OF AUTOPHAGY AND NEUROINFLAMMATION IN THE ACUTE PERIOD OF ATEROTHROMBOTIC ISCHEMIC STROKE



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Abstract

Abstract

Postischemic neuroinflammation is a critical pathophysiological process within the entire pattern of cerebral ischemia. It is characterized by microglial and astroglial activation and is accompanied by disturbances in the innate and adaptive immune response. The early damage of the blood-brain barrier (BBB) integrity is accompanied by the brain autoantigens release into circulation, in particular, the neurospecific protein S100B. According to recent experimental data, activated autophagy is associated with postischemic neuroinflammation, involved in its regulation and influences the outcome of the ischemic stroke (IS) acute period. Experimental evidence is provided for the autophagy involvement in the regulation of proinflammatory cytokines and chemokines production. The influence of activated autophagy on the pro- and anti-inflammatory cytokines balance in acute IS has been demonstrated. Purpose of the study: to quantitatively evaluate key autophagy biomarkers, the early biomarker of BBB damage S100B, pro- and anti-inflammatory cytokines in the dynamics of the IS acute period. To identify the relationship between autophagy and inflammation biomarkers. 112 patients with acute IS and 56 healthy persons were examined. Patients underwent dynamic clinical neurological examination and blood testing on the 1st, 7th and 14th days from the disease’s onset. The level of autophagy in peripheral blood leukocytes was determined by flow cytometry by assessing the intracellular expression of autophagy proteins LC3, p62 and mean fluorescence intensity of the Cyto-ID dye, which specifically recognizes active autophagosomes. Serum concentration of TNFα, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-18, neuropeptide S100B and autophagy biomarkers Beclin-1, LC3, p62 were determined by ELISA. A statistically significant increase in the studied biomarkers was found compared to the control group. The maximum increase in inflammation indicators and neuropeptide S100B was observed on the 1st, and autophagy biomarkers – on the 7th day of the disease. Established correlations indicate the participation of activated autophagy in the postischemic neuroinflammation regulation and its involvement in ischemic brain damage in the early stages of the IS acute period (days 1–7).

About the authors

Anna Vladimirovna Lugovaya

Pavlov First St Petersburg State Medical University, Saint Petersburg, Russian Federation;
St. Petersburg Institute of Bioregulation and Gerontology, North-Western Branch, Russian Academy of Sciences, St. Petersburg, Russian Federation.

Email: lugovaya2710spb@icloud.com
ORCID iD: 0000-0002-7690-9064
SPIN-code: 4350-2349
ResearcherId: KFT-9408-2024

 PhD (Medicine), Clinical Аllergist-Immunologist, Clinical Laboratory Diagnostition, Assistant of the Department of Clinical Laboratory Diagnostics with a Course in Molecular Medicine, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russian Federation, Senior Researcher of the Research Center "St. Petersburg Institute of Bioregulation and Gerontology" of the North-Western Branch of the Russian Academy of Sciences, St. Petersburg, Russia

Russian Federation, 197022, St. Petersburg, L'va Tolstogo str. 6/8, building №11

Natalia Mikhailovna Kalinina

Pavlov First St Petersburg State Medical University, Saint Petersburg, Russian Federation;
Nikiforov Russian Center of Emergency and Radiation Medicine, Saint Petersburg, Russian Federation

Email: doctkalin@mail.ru
ORCID iD: 0000-0003-1752-6888
SPIN-code: 3399-4781

Natalia Mikhailovna Kalinina, PhD, MD (Medicine), Professor, Department of Immunology, Pavlov First Saint Petersburg State Medical University, Leading Research Associate, Nikiforov Russian Center of Emergency and Radiation Medicine, Saint Petersburg

Russian Federation, 197022, St. Petersburg, L'va Tolstogo str. 6/8; 197082, St. Petersburg, st. Optikov, 54

Andrei Mikhailovich Ivanov

S.M. Kirov Military Medical Academy, St. Petersburg

Email: iamvma@mail.com
ORCID iD: 0000-0002-8899-7524
SPIN-code: 6971-1744

PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Head, Department of Clinical Biochemistry and Laboratory Diagnostics, S.M. Kirov Military Medical Academy

Russian Federation, 194044, St. Petersburg, Academician Lebedev street, 6, lit. G

Yuri Vladimirovich Nikitin

S.M. Kirov Military Medical Academy, St. Petersburg

Email: dr.iuriinikitin@gmail.com
ORCID iD: 0000-0001-7892-2783
SPIN-code: 5911-6267

Clinical Allergologist-Immunologist, Center of Clinical Laboratory Diagnostics; Lecturer, Department of Clinical Biochemistry and Laboratory Diagnostics, S.M. Kirov Military Medical Academy, St. Petersburg

Russian Federation, 194044, St. Petersburg, Academician Lebedev street, 6, lit. G

Irina Alexandrovna Sukhina

S.M. Kirov Military Medical Academy, St. Petersburg, Russian Federation

Email: kinya2000@mail.ru
ORCID iD: 0000-0003-1984-2497
SPIN-code: 5606-4874

PhD (Biology), Lecturer, Department of Clinical Biochemistry and Laboratory Diagnostics, S.M. Kirov Military Medical Academy, St. Petersburg

Russian Federation, 194044, St. Petersburg, Academician Lebedev street, 6, lit. G

Vladimir Phylippovich Mitreikin

Pavlov First St Petersburg State Medical University, Saint Petersburg, Russian Federation

Email: mvphch2742@mail.ru
ORCID iD: 0000-0001-5977-8907
SPIN-code: 3305-9570

PhD, MD (Medicine), Professor, Department of Pathological Physiology, Pavlov First Saint Petersburg State Medical University, Saint Petersburg

197022, St. Petersburg, L'va Tolstogo str. 6/8, administrative building

Sergey Shamilevich Zabirov Shamilevich Zabirov

City Clinical Hospital of St. Luke, Saint Petersburg; Russian Federation

Email: info@lucaclinic.ru
ORCID iD: 0000-0001-6348-0759
SPIN-code: 7386-9871

hD (Medicine), Head of the Center for Medical Rehabilitation and Head of the Department of Medical Rehabilitation of Adults with CNS Disabilities, Neurologist, Member of the Union of Rehabilitologists of Russia; Saint Petersburg

Russian Federation, 195009, St. Petersburg, Russia, Chugunnaya street, 46

German Eduardovich Kirilkin

Pavlov First St Petersburg State Medical University, Saint Petersburg, Russian Federation

Author for correspondence.
Email: germankirilkin@gmail.com
ORCID iD: 0000-0001-8913-984X
SPIN-code: 9570-4676

Clinical Resident of the Department of Clinical Laboratory Diagnostics with a Course of Molecular Medicine

Russian Federation, 197022, St. Petersburg, L'va Tolstogo str. 6/8, building №11

References

  1. Lugovaya A.V., Kalinina, N.M., Ivanov A.M., Nikitin Yu. V., Sukhina I.А., Mitreikin V.Ph., Semenova E.V. Identification of the relationship between biomarkers of autophagy, apoptosis and inflammation in the acute period of atherothrombotic ischemic stroke. Meditsinskaya Immunologiya = Medical Immunology, 2023, Vol. 25, no. 4, pp. 939-946. (In Russ.)
  2. Chen R., Jiang M., Li B., Zhong W., Wang Z., Yuan W., Yan J. The role of autophagy in pulmonary hypertension: a double-edge sword. Apoptosis, 2018, Vol. 23, no. 9, pp. 459-469.[doi: 10.1007/s10495-018-1477-4]
  3. Guimarães de Almeida Barros A., Roquim E Silva L., Pessoa A., Eiras Falcão A., Viana Magno L.A., Valadão Freitas Rosa D., Aurelio Romano Silva M., Marques de Miranda D., Nicolato R. Use of biomarkers for predicting a malignant course in acute ischemic stroke: an observational case-control study. Sci. Rep. 2023, Vol. 13, no. 1, 16097. [doi: 10.1038/s41598-023-43408-z]
  4. Hu K., Gao Y., Chu S., Chen N. Review of the effects and Mechanisms of microglial autophagy in ischemic stroke. Int. Immunopharmacol., 2022, Vol. 108, 108761. [10.1016/j.intimp.2022.108761]
  5. Jiang C.T., Wu W.F., Deng Y.H., Ge J.W. Modulators of microglia activation and polarization in ischemic stroke (Review). Mol. Med. Rep., 2020, Vol. 21, no. 5, pp. 2006-2018. [doi: 10.3892/mmr.2020.11003]
  6. Lasek-Bal A., Jedrzejowska-Szypulka H., Student S., Warsz-Wianecka A., Zareba K., Puz P., Bal W., Pawletko K., Lewin-Kowalik J. The importance of selected markers of inflammation and blood-brain barrier damage for short-term ischemic stroke prognosis. J. Physiol. Pharmacol., 2019, Vol. 70, no. 2, pp. 209-217.[doi: 10.26402/jpp.2019.2.04]
  7. Li H., Qiu S., Li X., Li M., Peng Y. Autophagy biomarkers in CSF correlates with infarct size, clinical severity and neurological outcome in AIS patients. J. Transl. Med. 2015. Vol. 13. P. 359. [doi: 10.1186/s12967-015-0726-3]
  8. Li R., Fan W., Li D., Liu X. Correlation of common inflammatory cytokines with cognition impairment, anxiety, and depression in acute ischemic stroke patients. Braz. J. Med. Biol. Res., 2022, Vol. 55: e11517.[doi: 10.1590/1414-431X2021e11517]
  9. Lu X., Zhang J., Ding Y., Wu J., Chen G. Novel Therapeutic Strategies for Ischemic Stroke: Recent Insights into Autophagy. Oxidative Medicine and Cellular Longevity, 2022, Vol. 2022, 3450207.[doi: 10.1155/2022/3450207]
  10. Mo Y., Sun Y.Y., Liu K.Y. Autophagy and inflammation in ischemic stroke. Neural Regen. Res. 2020, Vol. 15 no. 8, pp. 1388-1396. [doi: 10.4103/1673-5374.274331]
  11. Tsygan N.V., Trashkov A.P., Litvinenko I.V., Yakovleva V.A., Ryabtsev A.V., Vasiliev A.G., Churilov L.P. Autoimmunity in acute ischemic stroke and the role of blood–brain barrier: the dark side or the light one? Front. Med., 2019, Vol. 13, no. 4, pp. 420-426.[doi: 10.1007/s11684-019-0688-6]
  12. Qin X., Akter F., Qin L., Cheng J., Guo M., Yao S., Jian Z., Liu R., Wu S. Adaptive Immunity Regulation and Cerebral Ischemia. Front. Immunol., 2020, Vol. 11, 689.[doi: 10.3389/fimmu.2020.00689]
  13. Zhu H., Hu S., Li Y., Sun Y., Xiong X., Hu X., Chen J., Qiu S. Interleukins and Ischemic Stroke. Front. Immunol., 2022, Vol. 13, 828447.[doi: 10.3389/fimmu.2022.828447]
  14. Zhu H., Hu S., Li Y., Sun Y., Xiong X., Hu X., Chen J., Qiu S. Interleukins and Ischemic Stroke. Front. Immunol., 2022, Vol. 13, 828447.[doi: 10.3389/fimmu.2022.828447]

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Copyright (c) Lugovaya A., Kalinina N.M., Ivanov A.M., Nikitin Y.V., Sukhina I.A., Mitreikin V.P., Zabirov S.S., Kirilkin G.E.

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