A personalized approach to the correction of age-dependent endothelial dysfunction in patients with cerebrovascular diseases

The role of endothelial damage as the main pathological mechanism of a number of diseases has been studied for a long time, but in the context of identifying new risk factors for CVD (viruses, genetic mutations, congenital dysplasia, autoimmune diseases), the problem of personalized cerebroprotection, taking into account the age and state of the endothelium, becomes relevant. Currently, the stage and age dependence of the development of endothelial dysfunction has been proven. Endothelial aging is a predictor of the development of cardiovascular diseases, and it can manifest itself depending on the patient’s age and the presence of comorbidity both in the direction of vasoconstriction and prothrombotic changes, and in the direction of loss of autoregulation of vasodilation and activation of oxidative stress, changes in the concentration of glucose, lipids and immune cell infiltration. Accordingly, drug correction of endothelial dysfunction should be personalized, age-oriented. The use of nicotinoyl gammaaminobutyric acid preparations, including those combined with Ginkgo Biloba extract, can be considered as a model for choosing the correction of age-dependent endothelial dysfunction in patients with cerebrovascular diseases. In young patients, the onset of endothelial dysfunction is characterized by changes in blood pressure (fluctuations from high to low numbers and vice versa), severe asthenia, headaches, mild cognitive and autonomic disorders, so at the initial stage, preference is given to a fixed combination of nicotinoyl gamma-aminobutyric acid with Ginkgo Biloba extract. In middle-aged and older patients with a long history of hypertension, stroke, and TIA in the anamnesis, it is advisable to begin therapy with parenteral forms of nicotinoyl gamma-aminobutyric acid, followed by oral administration, which will provide a prolonged effect and a more pronounced therapeutic effect.

1. Zhou M, Shen H. Forecasting the global burden of disease to 2050. Lancet. 2024;403(10440):1961–1963. https://doi.org/10.1016/S01406736(24)009322.

2. Chew NWS, Ng CH, Tan DJH, Kong G, Lin C, Chin YH et al. The global burden of metabolic disease: Data from 2000 to 2019. Cell Metab. 2023;35(3):414–428. https://doi.org/10.1016/j.cmet.2023.02.003.

3. Putilina MV, Mutovina ZYu, Kurushina OV, Khalilova DM, Saverskaya EN, Stepanova SB et al. Determination of the prevalence of postcovid syndrome and assessment of the effectiveness of the drug Cortexin in the treatment of neurological disorders in patients with postcovid syndrome. Results of the multicenter clinical and epidemiological observational program CORTEX. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2022;122(1):84–90. (In Russ.) https://doi.org/10.17116/jnevro202212201184.

4. Iba A, Hosozawa M, Hori M, Muto Y, Muraki I, Masuda R et al. Prevalence of and Risk Factors for Post–COVID-1 9 Condition during Omicron BA.5–Dominant Wave, Japan. Emerg Infect Dis. 2024;30(7):1380–1389. https://doi.org/10.3201/eid3007.231723.

5. Fernándezde Las Peñas C, Raveendran AV, Giordano R, Arendt Nielsen L. Long COVID or Post COVID19 Condition: Past, Present and Future Research Directions. Microorganisms. 2023;11(12):2959. https://doi.org/10.3390/microorganisms11122959.

6. Nehme M, Vetter P, Chappuis F, Kaiser L, Guessous I. Prevalence of PostCoronavirus Disease Condition 12 Weeks After Omicron Infection Compared With Negative Controls and Association With Vaccination Status. Clin Infect Dis. 2023;76(9):1567–1575. https://doi.org/10.1093/cid/ciac947.

7. Gallo G, Savoia C. New Insights into Endothelial Dysfunction in Cardiometabolic Diseases: Potential Mechanisms and Clinical Implications. Int J Mol Sci. 2024;25(5):2973. https://doi.org/10.3390/ijms25052973.

8. Putilina MV. Endothelium – as target for new therapeutic strategies in cerebral vascular diseases. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2017;117(10):122–130. (In Russ.) https://doi.org/10.17116/jnevro2017117101122130.

9. Corban MT, Lerman LO, Lerman A. Endothelial dysfunction cardiovascular disease pathophysiology hidden in plain sight. Arterioscler Thromb Vasc Biol. 2019;39(7):1272–1274. https://doi.org/10.1161/ATVBAHA.119.312836.

10. Kolib ЕМ, Ali DA. How Would Metabolic Syndrome Disturb the Normal Endothelial Function? In: Uzun H, Dumur S. Metabolic syndrome: a comprehensive update with new insights. Bentham Science Publishers; 2025, pp. 127–131.. https://doi.org/10.2174/9789815322132125010010.

11. Gallo G, Savoia C. New Insights into Endothelial Dysfunction in Cardiometabolic Diseases: Potential Mechanisms and Clinical Implications. Int J Mol Sci. 2024;25(5):2973. https://doi.org/10.3390/ijms25052973.

12. Santoro L, Zaccone V, Falsetti L, Ruggieri V, Danese M, Miro C et al. Role of Endothelium in Cardiovascular Sequelae of Long COVID. Biomedicines. 2023;11(8):2239. https://doi.org/10.3390/biomedicines11082239.

13. Han Y, Kim SY. Endothelial senescence in vascular diseases: current understanding and future possibilities of senotherapy. Exp Mol Med. 2023;55(1):1–12. https://doi.org/10.1038/s1227602200906w.

14. Putilina MV. Current concepts about small vessel disease. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2019;119(11):65–73. (In Russ.) https://doi.org/10.17116/jnevro201911911165.

15. Fedin AI, Starykh EP, Putilin MV, Starykh EV, Mironova OP, Badalyan KR. Endothelial dysfunction in patients with chronic cerebral ischemia and the possibilities of its pharmacological correction. Lechaschi Vrach. 2015;(5):15–18. (In Russ.) Available at: https://www.lvrach.ru/2015/05/15436219.

16. Wijdicks EFM. Identifying encephalopathies from acute metabolic derangements. J Intern Med. 2022;292(6):846–857. https://doi.org/10.1111/joim.13538.

17. Lyden PD. Cerebroprotection for Acute Ischemic Stroke: Looking Ahead. Stroke. 2021;52(9):3033–3044. https://doi.org/10.1161/STROKEAHA.121.032241.

18. Putilina MV. A young patient at a neurologist’s appointment: features of diagnostics and therapy. Meditsinskiy Sovet. 2023;(10):146–152. (In Russ.) https://doi.org/10.21518/ms2023225.

19. Bai C, Wang Z, Stone C, Zhou D, Ding J, Ding Y et al. Pathogenesis and Management in Cerebrovenous Outflow Disorders. Aging Dis. 2021;12(1):203–222. https://doi.org/10.14336/AD.2020.0404.

20. Gognieva DG, Shchekochikhin DYu, Gavrilova EV, Syrkina EA, Bogdanova RS, Syrkin AL, Kopylov FYu. The problem of adherence to treatment in general medical practice. Kardiologiya i Serdechno Sosudistaya Khirurgiya. 2019;12(6):510–515. (In Russ.) https://doi.org/10.17116/ardio201912061510.

21. Mitrokhin KV, Baranishin AA, Mitrohin KV, Baranishin AA. Classification and brief description of drug analogues, derivatives of gammaaminobutyric acid and toxic substances influencing GABAergic connections. Russian Journal of Anеsthesiology and Reanimatology. 2018;(6):22–30. (In Russ.) https://doi.org/10.17116/anesthesiology201806122.

22. Smirnova AA, Zhivolupov SA. Pathogenetic mechanisms of cognitive impairment in cerebrovascular pathology and prospects for their correction using nootropic and neuroprotective agents. Meditsinskiy Sovet. 2023;17(6):85–93. (In Russ.) https://doi.org/10.21518/ms2023099.

23. Putilina MV, Teplova NV. Algorithms of rational therapy for chronic cerebral ischemia. Nervous Diseases. 2019;(1):10–16. (In Russ.) https://doi.org/10.24411/20715315201812074.

24. Noor E-Tabassum, Das R, Lami MS, Chakraborty AJ, Mitra S, Tallei TE et al. Ginkgo biloba: A Treasure of Functional Phytochemicals with Multimedicinal Applications. Evid Based Complement Alternat Med. 2022;2022:8288818. https://doi.org/10.1155/2022/8288818.

25. Abdel Zaher AO, Farghaly HSM, El Refaiy AEM, Abd Eldayem AM. Protective effect of the standardized extract of ginkgo biloba (EGb761) against hypertension with hypercholesterolemia induced renal injury in rats: Insights in the underlying mechanisms. Biomed Pharmacother. 2017;95:944–955. https://doi.org/10.1016/j.biopha.2017.08.078.

26. Aziz TA, Hussain SA, Mahwi TO, Ahmed ZA, Rahman HS, Rasedee A. The efficacy and safety of Ginkgo biloba extract as an adjuvant in type 2 diabetes mellitus patients ineffectively managed with metformin: a double blind, randomized, placebo controlled trial. Drug Des Devel Ther. 2018;12:735–742. https://doi.org/10.2147/DDDT.S157113.

27. Zakharov VV, Borodulina IV, Vakhnina NV. Treatment of patients with chronic cerebral ischemia: experience of using the combined neuroprotective drug Picamilon Ginkgo. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2022;122(9):95–103. (In Russ.) https://doi.org/10.17116/jnevro202212209195.

28. Putilina M. Combined neuroprotective therapy for cerebrovascular diseases. Vrach. 2012;(4):69–73. (In Russ.)

29. Putilina MV. Neuroplasticity as a basis for early rehabilitation of stroke patients. Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(12–2):64–69. (In Russ.) Available at: https://pubmed.ncbi.nlm.nih.gov/22792752.

30. Ali DN, Ali HM, Lopez MR, Kang S, Choi DS. Astrocytic GABAergic Regulation in Alcohol Use and Major Depressive Disorders. Cells. 2024;13(4):318. https://doi.org/10.3390/cells13040318.

31. Maida CD, Norrito RL, Rizzica S, Mazzola M, Scarantino ER, Tuttolomondo A. Molecular pathogenesis of ischemic and hemorrhagic strokes: background and therapeutic approaches. Int J Mol Sci. 2024;25(12):6297. https://doi.org/10.3390/ijms25126297.

32. Danilov AB, Shindryaeva NN, Borodulina IV, Lunegov TD, Kristeleva DA. Clinical efficacy and safety of Picamilon in patients with progressive chronic cerebral ischemia. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2024;124(8):71–80. (In Russ.) https://doi.org/10.17116/jnevro202412408171.

33. Danilov AB, Shindryaeva NN, Borodulina IV, Lunegov TD. Integrative assessment of the effectiveness and safety of outpatient use of Picamilon. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2024;124(7):119–130. (In Russ.) https://doi.org/10.17116/jnevro2024124071119.

34. Smirnova AA, Zhivolupov SA. Pathogenetic mechanisms of cognitive impairment in cerebrovascular pathology and prospects for their correction using nootropic and neuroprotective agents. Meditsinskiy Sovet. 2023;(6):85–93. (In Russ.) https://doi.org/10.21518/ms2023-099.

35. Putilina MV, Teplova NV. Drug safety as a priority area of domestic medicine. Lechebnoe Delo. 2019;(4):7–14. (In Russ.) https://doi.org/10.24411/20715315201912152.