Morphological peculiarities of revascularization of perifocal areas of brain infarction

Authors

DOI:

https://doi.org/10.14739/2310-1237.2023.3.286132

Keywords:

perifocal areas of brain infarction, revascularization, CD34, CD105, astrocytes

Abstract

Aim. To study pathomorphological signs of revascularization of perifocal areas of brain infarction in the dynamics of the acute period of the disease.

Material and methods. Perifocal areas of brain infarction in patients who died at the 1st, 3rd, 7th, and 14th days were studied. General histopathological study was followed by 10 % ammonium silver impregnation and immunohistochemical examination using monoclonal antibodies Mo a-Hu CD34, Clone QBEnd/10 (“Thermo Fisher Scientific Inc.” – USA) and Mo a-Hu CD105 Endoglin were used. clone: SN6h1 (“DAKO”, Denmark). Vascular density and total cross-sectional area of vessels were studied. For the morphometric study, Videotest – Morphology 5.2.0.158 software (VideoTest LLC) was used. Statistical processing of the obtained data was carried out using the Statistica® for Windows 13.0 software.

Results. According to the data of CD34 expression, from the 3rd day in the perifocal areas of brain infarction, the angiogenesis processes were increased: the density of blood vessels increased by 18.48 %, and the total cross-sectional area of vessels increased by 1.93 times. On the 7th day, the maximal vessel density and total cross-sectional area of vessels were registered in these areas; there was a vascular budding, formation of endothelial proliferates, and increased expression of CD105 on the vascular endothelium and pericytes, which indicates the active participation of the latter in angiogenesis. On the 14th day, blood vessel density and indicators of the total cross-sectional area of vessels decreased. During this period, the density of the astrocytes increased in the infarct’s perifocal areas with hypertrophy of their bodies and processes.

Conclusions. According to CD34 and CD105 expression data, in the perifocal areas of cerebral infarction, the processes of angiogenesis gradually increase from the 3rd day manifesting by increase in the blood vessel density and total vascular cross-sectional area, as well as in the vascular budding and the formation of endothelial proliferates. Vascular remodeling is accompanied by increased density and hypertrophy of astroglia in the perifocal areas of cerebral infarction.

 

Author Biographies

S. I. Tertyshnyi, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, PhD, DSc, Professor, Head of the Department of Pathological Anatomy and Forensic Medicine

О. О. Voloshanska, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

MD, Assistant of the Department of Pathological Anatomy and Forensic Medicine

А. М. Serheieva, Zaporizhzhia State Medical and Pharmaceutical University, Ukraine

Assistant of the Department of Pathological Anatomy and Forensic Medicine

References

  1. King, D., Wittenberg, R., Patel, A., Quayyum, Z., Berdunov, V., & Knapp, M. (2020). The future incidence, prevalence and costs of stroke in the UK. Age and ageing, 49(2), 277-282. https://doi.org/10.1093/ageing/afz163
  2. Akinyemi, R. O., Ovbiagele, B., Adeniji, O. A., Sarfo, F. S., Abd-Allah, F., Adoukonou, T., Ogah, O. S., Naidoo, P., Damasceno, A., Walker, R. W., Ogunniyi, A., Kalaria, R. N., & Owolabi, M. O. (2021). Stroke in Africa: profile, progress, prospects and priorities. Nature reviews. Neurology, 17(10), 634-656. https://doi.org/10.1038/s41582-021-00542-4
  3. Millenaar, D., Ragoschke-Schumm, A., Fehlmann, T., Raible, M., Lochner, P., Böhm, M., Fassbender, K., Keller, A., Mahfoud, F., & Ukena, C. (2022). Ischemic Stroke-A Scientometric Analysis. Frontiers in neurology, 13, 893121. https://doi.org/10.3389/fneur.2022.893121
  4. Yang, Y., & Torbey, M. T. (2020). Angiogenesis and Blood-Brain Barrier Permeability in Vascular Remodeling after Stroke. Current neuropharmacology, 18(12), 1250-1265. https://doi.org/10.2174/1570159X18666200720173316;
  5. Williamson, M. R., Franzen, R. L., Fuertes, C. J. A., Dunn, A. K., Drew, M. R., & Jones, T. A. (2020). A Window of Vascular Plasticity Coupled to Behavioral Recovery after Stroke. The Journal of neuroscience, 40(40), 7651-7667. https://doi.org/10.1523/JNEUROSCI.1464-20.2020
  6. Ma, Y., Yang, S., He, Q., Zhang, D., & Chang, J. (2021). The Role of Immune Cells in Post-Stroke Angiogenesis and Neuronal Remodeling: The Known and the Unknown. Frontiers in immunology, 12, 784098. https://doi.org/10.3389/fimmu.2021.784098
  7. Sun, P., Zhang, K., Hassan, S. H., Zhang, X., Tang, X., Pu, H., Stetler, R. A., Chen, J., & Yin, K. J. (2020). Endothelium-Targeted Deletion of microRNA-15a/16-1 Promotes Poststroke Angiogenesis and Improves Long-Term Neurological Recovery. Circulation research, 126(8), 1040-1057. https://doi.org/10.1161/CIRCRESAHA.119.315886
  8. Sargento-Freitas, J., Pereira, A., Gomes, A., Amorim, P., Matos, T., Cardoso, C. M. P., Silva, F., Santo, G. C., Nunes, C., Galego, O., Carda, J., Branco, J., Lourenço, V., Cunha, L., & Ferreira, L. (2018). STROKE34 Study Protocol: A Randomized Controlled Phase IIa Trial of Intra-Arterial CD34+ Cells in Acute Ischemic Stroke. Frontiers in neurology, 9, 302. https://doi.org/10.3389/fneur.2018.00302
  9. Bachelier, K., Bergholz, C., & Friedrich, E. B. (2020). Differentiation potential and functional properties of a CD34 CD133+ subpopulation of endothelial progenitor cells. Molecular medicine reports, 21(1), 501-507. https://doi.org/10.3892/mmr.2019.10831
  10. Matta, A., Nader, V., Galinier, M., & Roncalli, J. (2021). Transplantation of CD34+ cells for myocardial ischemia. World journal of transplantation, 11(5), 138-146. https://doi.org/10.5500/wjt.v11.i5.138
  11. Kukumberg, M., Zaw, A. M., Wong, D. H. C., Toh, C. M., Chan, B. P. L., Seet, R. C. S., Wong, P. T. H., & Yim, E. K. F. (2021). Characterization and Functional Assessment of Endothelial Progenitor Cells in Ischemic Stroke Patients. Stem cell reviews and reports, 17(3), 952-967. https://doi.org/10.1007/s12015-020-10064-z
  12. Rodríguez-Esparragón, F., Torres-Mata, L. B., López-Fernández, J. C., Cappiello, L., González-Martín, J. M., Clavo, B., Serna-Gómez, J. A., Estupiñán-Quintana, L., Torres-Ascensión, C., & Villar, J. (2022). Clinical relevance of circulating angiogenic cells in patients with ischemic stroke. BMC cardiovascular disorders, 22(1), 118. https://doi.org/10.1186/s12872-021-02421-8
  13. Zhou, S. Y., Guo, Z. N., Zhang, D. H., Qu, Y., & Jin, H. (2022). The Role of Pericytes in Ischemic Stroke: Fom Cellular Functions to Therapeutic Targets. Frontiers in molecular neuroscience, 15, 866700. https://doi.org/10.3389/fnmol.2022.866700
  14. He, T., Yang, G. Y., & Zhang, Z. (2022). Crosstalk of Astrocytes and Other Cells during Ischemic Stroke. Life, 12(6), 910. https://doi.org/10.3390/life12060910
  15. Voloshanska, O. (2021). Patomorfolohichni proiavy sudynnoho remodeliuvannia v peryfokalnykh diliankakh ishemichnykh infarktiv mozku [Pathomorphological manifestations of vascular remodeling in the perifocal areas of ischemic cerebral infarction]. Bukovynskyi medychnyi visnyk, 25(2), 22-28. [in Ukrainian]. https://doi.org/10.24061/2413-0737.XXV.2.98.2021.4
  16. Weidner, N. (1999). Tumour vascularity and proliferation: clear evidence of a close relationship. The Journal of pathology, 189(3), 297-299. https://doi.org/10.1002/(SICI)1096-9896(199911)189:3<297::AID-PATH434>3.0.CO;2-O
  17. Kanazawa, M., Takahashi, T., Ishikawa, M., Onodera, O., Shimohata, T., & Del Zoppo, G. J. (2019). Angiogenesis in the ischemic core: A potential treatment target?. Journal of cerebral blood flow and metabolism, 39(5), 753-769. https://doi.org/10.1177/0271678X19834158
  18. Xue, L. X., Shu, L. Y., Wang, H. M., Lu, K. L., Huang, L. G., Xiang, J. Y., Geng, Z., Zhao, Y. W., & Chen, H. (2023). miR-181b promotes angiogenesis and neurological function recovery after ischemic stroke. Neural regeneration research, 18(9), 1983-1989. https://doi.org/10.4103/1673-5374.367957
  19. Alrafiah, A., Alofi, E., Almohaya, Y., Hamami, A., Qadah, T., Almaghrabi, S., Hakami, N., Alrawaili, M. S., & Tayeb, H. O. (2021). Angiogenesis Biomarkers in Ischemic Stroke Patients. Journal of inflammation research, 14, 4893-4900. https://doi.org/10.2147/JIR.S331868
  20. Wlodarczyk, L., Szelenberger, R., Cichon, N., Saluk-Bijak, J., Bijak, M., & Miller, E. (2021). Biomarkers of Angiogenesis and Neuroplasticity as Promising Clinical Tools for Stroke Recovery Evaluation. International journal of molecular sciences, 22(8), 3949. https://doi.org/10.3390/ijms22083949
  21. Hatakeyama, M., Ninomiya, I., & Kanazawa, M. (2020). Angiogenesis and neuronal remodeling after ischemic stroke. Neural regeneration research, 15(1), 16-19. https://doi.org/10.4103/1673-5374.264442
  22. Voloshanska, О. О., & Tertyshnyi, S. I. (2020). Patomorfolohichni zminy sudynnoho rusla ta stan kolateralnoho krovotoku pry mozkovykh infarktakh [Pathomorphological changes of the vascular bed and the state of collateral blood flow in cerebral infarction]. Pathologia, 17(2), 234-240. https://doi.org/10.14739/2310-1237.2020.2.212808
  23. Gregorius, J., Wang, C., Stambouli, O., Hussner, T., Qi, Y., Tertel, T., Börger, V., Mohamud Yusuf, A., Hagemann, N., Yin, D., Dittrich, R., Mouloud, Y., Mairinger, F. D., Magraoui, F. E., Popa-Wagner, A., Kleinschnitz, C., Doeppner, T. R., Gunzer, M., Meyer, H. E., Giebel, B., Hermann, D. M. (2021). Small extracellular vesicles obtained from hypoxic mesenchymal stromal cells have unique characteristics that promote cerebral angiogenesis, brain remodeling and neurological recovery after focal cerebral ischemia in mice. Basic research in cardiology, 116(1), 40. https://doi.org/10.1007/s00395-021-00881-9
  24. Kishida, N., Maki, T., Takagi, Y., Yasuda, K., Kinoshita, H., Ayaki, T., Noro, T., Kinoshita, Y., Ono, Y., Kataoka, H., Yoshida, K., Lo, E. H., Arai, K., Miyamoto, S., & Takahashi, R. (2019). Role of Perivascular Oligodendrocyte Precursor Cells in Angiogenesis After Brain Ischemia. Journal of the American Heart Association, 8(9), e011824. https://doi.org/10.1161/JAHA.118.011824
  25. Mangiardi, M., Bonura, A., Iaccarino, G., Alessiani, M., Bravi, M. C., Crupi, D., Pezzella, F. R., Fabiano, S., Pampana, E., Stilo, F., Alfano, G., & Anticoli, S. (2023). The Pathophysiology of Collateral Circulation in Acute Ischemic Stroke. Diagnostics, 13(14), 2425. https://doi.org/10.3390/diagnostics13142425
  26. Krupinski, J., Kaluza, J., Kumar, P., Kumar, S., & Wang, J. M. (1994). Role of angiogenesis in patients with cerebral ischemic stroke. Stroke, 25(9), 1794-1798. https://doi.org/10.1161/01.str.25.9.1794
  27. Li, J., Ma, Y., Miao, X. H., Guo, J. D., & Li, D. W. (2021). Neovascularization and tissue regeneration by endothelial progenitor cells in ischemic stroke. Neurological sciences, 42(9), 3585-3593. https://doi.org/10.1007/s10072-021-05428-3
  28. Shimizu, Y., Kawashiri, S. Y., Kiyoura, K., Koyamatsu, J., Fukui, S., Tamai, M., Nobusue, K., Yamanashi, H., Nagata, Y., & Maeda, T. (2020). Circulating CD34+ cells and active arterial wall thickening among elderly men: A prospective study. Scientific reports, 10(1), 4656. https://doi.org/10.1038/s41598-020-61475-4
  29. Rudnicka-Drożak, E., Drożak, P., Mizerski, G., & Drożak, M. (2022). Endothelial Progenitor Cells in Neurovascular Disorders-A Comprehensive Overview of the Current State of Knowledge. Biomedicines, 10(10), 2616. https://doi.org/10.3390/biomedicines10102616
  30. Hassanpour, M., Salybekov, A. A., Kobayashi, S., & Asahara, T. (2023). CD34 positive cells as endothelial progenitor cells in biology and medicine. Frontiers in cell and developmental biology, 11, 1128134. https://doi.org/10.3389/fcell.2023.1128134
  31. Núñez-Gómez, E., Pericacho, M., Ollauri-Ibáñez, C., Bernabéu, C., & López-Novoa, J. M. (2017). The role of endoglin in post-ischemic revascularization. Angiogenesis, 20(1), 1-24. https://doi.org/10.1007/s10456-016-9535-4
  32. Haarmann, A., Zimmermann, L., Bieber, M., Silwedel, C., Stoll, G., & Schuhmann, M. K. (2022). Regulation and Release of Vasoactive Endoglin by Brain Endothelium in Response to Hypoxia/Reoxygenation in Stroke. International journal of molecular sciences, 23(13), 7085. https://doi.org/10.3390/ijms23137085
  33. Cao, L., Zhou, Y., Chen, M., Li, L., & Zhang, W. (2021). Pericytes for Therapeutic Approaches to Ischemic Stroke. Frontiers in neuroscience, 15, 629297. https://doi.org/10.3389/fnins.2021.629297
  34. Williamson, M. R., Fuertes, C. J. A., Dunn, A. K., Drew, M. R., & Jones, T. A. (2021). Reactive astrocytes facilitate vascular repair and remodeling after stroke. Cell reports, 35(4), 109048. https://doi.org/10.1016/j.celrep.2021.109048

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Published

2023-12-22

How to Cite

1.
Tertyshnyi SI, Voloshanska ОО, Serheieva АМ. Morphological peculiarities of revascularization of perifocal areas of brain infarction. Pathologia [Internet]. 2023Dec.22 [cited 2026May25];20(3):243-9. Available from: https://pat.zsmu.edu.ua/article/view/286132

Issue

Vol. 20 No. 3 (2023)

Section

Original research

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