2026 / 01

DOI: 10.24075/brsmu.2026.008
Copyright: © 2026 by the authors. Licensee: Pirogov University.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (CC BY).

ORIGINAL RESEARCH

Assessing functional activity of microglia and macrophages in barrier-associated brain areas of spontaneously hypertensive rats

Razenkova VA , Korzhevskii DE
About authors

Institute of Experimental Medicine, Saint Petersburg, Russia

Correspondence should be addressed: Valeria A. Razenkova
Akademika Pavlova, 12, Saint Petersburg, 197376, Russia; ur.xednay@zar.ayirelav

About paper

Funding: the study received financil support from the Russian Science Foundation, project No. 24-15-00032, https://rscf.ru/en/project/24-15-00032/

Author contribution: Razenkova VA — setting up immunohistochemistry reactions, interpretation of results, image manipulation, manuscript writing; Korzhevskii DE — concept, study planning, literature review, manuscript editing.

Compliance with ethical standards: the study approved by the Ethics Committee of the Institute of Experimental Medicine (protocol No. 2/24 dated 25 April 2024) was conducted in accordance with provisions of the Declaration of Helsinki (2013)

Received: 2026-02-04 Accepted: 2026-02-21 Published online: 2026-02-28
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  1. Silvin A, Qian J, Ginhoux F. Brain macrophage development, diversity and dysregulation in health and disease. Cell Mol Immunol. 2023; 20: 1277–89.
  2. Li Q, Barres BA. Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. 2017; 18 (4): 225–42.
  3. Brioschi S, Zhou Y, Colonna M. Brain macrophages in development, homeostasis and disease. J Immunol [Internet]. 2020 Jan 15 [cited 2026 Jan 15]; 204 (2): 294. Available from: https://pmc. ncbi.nlm.nih.gov/articles/PMC7034672/.
  4. Mrdjen D, Pavlovic A, Hartmann FJ, Schreiner B, Utz SG, Leung BP, et al. High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease. Immunity [Internet]. 2018 Feb 20 [cited 2026 Jan 15]; 48 (2): 380–95.e6. Available from: https://www.sciencedirect.com/science/article/pii/S1074761318300323?via%3Dihub.
  5. Haruwaka K, Ikegami A, Tachibana Y, Ohno N, Konishi H, Hashimoto A, et al. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat Commun. 2019; 10 (1): 5816.
  6. Bisht K, Okojie KA, Sharma K, Lentferink DH, Sun Y-Y, Chen H-R, et al. Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice. Nat Commun. 2021; 12 (1): 5289.
  7. Taketomi T, Tsuruta F. Towards an understanding of microglia and border-associated macrophages. Biology (Basel). 2023 Aug 5; 12 (8): 1091.
  8. Engelhardt B, Vajkoczy P, Weller RO. The movers and shapers in immune privilege of the CNS. Nat Immunol. 2017; 18 (2): 123–31.
  9. Vara-Pérez M, Movahedi K. Border-associated macrophages as gatekeepers of brain homeostasis and immunity. Immunity. 2025; 58 (5): 1085–100.
  10. Greenberg SM, Bacskai BJ, Hernandez-Guillamon M, Pruzin J, Sperling R, van Veluw SJ. Cerebral amyloid angiopathy and Alzheimer disease — one peptide, two pathways. Nat Rev Neurol. 2020; 16 (1): 30–42.
  11. Amici SA, Dong J, Guerau-de-Arellano M. Molecular mechanisms modulating the phenotype of macrophages and microglia. Front Immunol. 2017; 8: 1520.
  12. Wan Y, Hua Y, Garton HJL, Novakovic N, Keep RF, Xi G. Activation of epiplexus macrophages in hydrocephalus caused by subarachnoid hemorrhage and thrombin. CNS Neurosci Ther. 2019; 25 (10): 1134–41.
  13. Kotova ММ, Apukhtin KV, Nikitin VS, Kalueff AV. On functional heterogeneity of micro- and astroglia. Russian Journal of Physiology. 2024; 110 (11): 1824–45. Russian.
  14. Tamura Y, Yamato M, Kataoka Y. Animal models for neuroinflammation and potential treatment methods. Front Neurol [Internet]. 2022 Jun 27 [cited 2026 Jan 15]; 13: 890217. Available from: www.frontiersin.org.
  15. Guzik TJ, Nosalski R, Maffia P, Drummond GR. Immune and inflammatory mechanisms in hypertension. Nat Rev Cardiol. 2024 Jun; 21 (6): 396–416.
  16. Fang Z, Shen G, Amin N, Lou C, Wang C, Fang M. Effects of neuroinflammation and autophagy on the structure of the blood– brain barrier in ADHD model. Neuroscience. 2023; 530: 17–25.
  17. Cohen EM, Mohammed S, Kavurma M, Nedoboy PE, Cartland S, Farnham MMJ, et al. Microglia in the RVLM of SHR have reduced P2Y12R and CX3CR1 expression, shorter processes, and lower cell density. Auton Neurosci Basic Clin. 2019; 216: 9–16.
  18. Guselnikova VV, Razenkova VA, Sufieva DA, Korzhevskii DE. Activation of microglia in the brain of spontaneously hypertensive rats. Bulletin of RSMU. 2023; (3): 49–55.
  19. Kulikova PV, Guselnikova VV. Morphological characterization of glial cells in the Substantia nigra of spontaneously hypertensive SHR rats. Medical academic journal. 2024; 24 (2): 93–9. Russian.
  20. Razenkova VA, Kirik OV., Korzhevskii DE. Microglia immunophenotyping in paraffin sections of the brain. Cell Tissue Biol. 2025; 19 (6): 597–604.
  21. Gonzalez-Marrero I, Hernández-Abad LG, Castañeyra-Ruiz L, Carmona-Calero EM, Castañeyra-Perdomo A. Changes in the choroid plexuses and brain barriers associated with high blood pressure and ageing. Neurol (English Ed). 2022; 37 (5): 371–82.
  22. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 2000; 164 (12): 6166–173.
  23. Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008; 8 (12): 958.
  24. Xue J, Schmidt S V., Sander J, Draffehn A, Krebs W, Quester I, et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity. 2014; 40 (2): 274–88.
  25. Ji Y, Li X, Yao X, Sun J, Yi J, Shen Y, et al. Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies. Front Immunol. 2025 Dec 12; 16: 1732718.
  26. Orihuela R, McPherson CA, Harry GJ. Microglial M1/M2 polarization and metabolic states. Br J Pharmacol. 2016; 173 (4): 649–65.
  27. Prinz M, Erny D, Hagemeyer N. Ontogeny and homeostasis of CNS myeloid cells. Nat Immunol. 2017; 18 (4): 385–92.
  28. Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014; 6:13.
  29. Rőszer T. Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm. 2015; 2015: 816460.
  30. Robles-Vera I, Toral M, de la Visitación N, Sánchez M, Gómez-Guzmán M, Muñoz R, et al. Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects. Br J Pharmacol. 2020; 177 (9): 2006–23.
  31. Zhao J, Lu N, Qu Y, Liu W, Zhong H, Tang N, et al. Calciumsensing receptor-mediated macrophage polarization improves myocardial remodeling in spontaneously hypertensive rats. Exp Biol Med (Maywood). 2024; 249: 10112.
  32. Böttcher C, Schlickeiser S, Sneeboer MAM, Kunkel D, Knop A, Paza E, et al. Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry. Nat Neurosci. 2019 Jan 17; 22 (1): 78–90.
  33. Mendoza-Mari Y, Stojanovic M, Miulli DE, Agrawal DK. Microglial response to inflammatory stimuli under electromagnetic field exposure. Arch Clin Biomed Res. 2025; 9 (4): 304–15.
  34. Cohen M, Ben-Yehuda H, Porat Z, Raposo C, Gordon S, Schwartz M. Newly formed endothelial cells regulate myeloid cell activity following spinal cord Injury via expression of CD200 ligand. J Neurosci. 2017; 37 (4): 972–85.
  35. Lively S, Wong R, Lam D, Schlichter LC. Sex- and development-dependent responses of rat microglia to pro- and anti-inflammatory stimulation. Front Cell Neurosci. 2018; 12: 433.
  36. Li L, Jiang W, Yu B, Liang H, Mao S, Hu X, et al. Quercetin improves cerebral ischemia/reperfusion injury by promoting microglia/macrophages M2 polarization via regulating PI3K/Akt/NF-κB signaling pathway. Biomed Pharmacother. 2023; 168: 115653.
  37. Paouri E, Tzara O, Kartalou G-I, Zenelak S, Georgopoulos S. Peripheral tumor necrosis factor-alpha (TNF-α) modulates amyloid pathology by regulating blood-derived immune cells and glial response in the brain of AD/TNF transgenic mice. J Neurosci. 2017; 37 (20): 5155–71.
  38. Chistiakov DA, Killingsworth MC, Myasoedova VA, Orekhov AN, Bobryshev Y V. CD68/macrosialin: not just a histochemical marker. Lab Invest. 2017; 97 (1): 4–13.
  39. Adler J, Parmryd I. Quantifying colocalization by correlation: The Pearson correlation coefficient is superior to the Mander’s overlap coefficient. Cytom Part A. 2010; 77A (8): 733–42.
  40. Ling E-A, Kaur C, Lu J. Origin, nature, and some functional considerations of intraventricular macrophages, with special reference to the epiplexus cells. Microsc Res Tech. 1998; 41: 43–56.
  41. Bolborea M, Dale N. Hypothalamic tanycytes: potential roles in the control of feeding and energy balance. Trends Neurosci. 2013; 36 (2): 91–100.