Immunohistochemical analysis of GFAP expression in the experimental sepsis-associated encephalopathy

Authors

DOI:

https://doi.org/10.14739/2310-1237.2021.3.240033

Keywords:

sepsis-associated encephalopathy, astroglial reactivity, GFAP

Abstract

Pathophysiology of sepsis-associated encephalopathy (SAE) is linked to blood-brain barrier breakdown, neuroinflammation and neurotransmitter imbalance in the brain. Astroglia, the most abundant cell population within the brain, plays the critical role in control of all kinds of homeostatic processes, thereby regulating the adaptive reactions of the brain to various challenges. Astroglia are highly heterogenous across the brain regions, therefore, damaging factors stimulate heterogenous astroglial reactivity and response in different brain regions.

The aim of this study was determining immunohistochemical features of GFAP expression in various brain regions in the model of rodent experimental sepsis.

Materials and methods. The experiment was performed in Wistar rats: control group of 5 sham-operated rats and the main group of 20 rats subjected to cecum ligation and puncture (CLP) procedure. The immunohistochemical study of GFAP expression in the sensorimotor cortex, subcortical white matter, hippocampal, thalamic and caudate nucleus/putamen regions was performed from 20 to 48 hours of the postoperative period.

Results. Starting from the 12th hour after CLP, animals began display progressive increase in signs of periorbital exudation, piloerection, fever-/hypothermia, diarrhea, social isolation, lethargy, and respiratory impairment. In the period of 20–38 hours, 9 animals showed expressed previously listed symptoms and were euthanized (CLP-B – lethal group), 11 rats survived until 48 hours of the experiment (CLP-A – survived group). In the lethal group, starting from 20 to 38 hours after the CLP procedure, a significant (relative to control) regionally-specific dynamic increase in the level of GFAP expression was observed in the brain: in the cortex – by 465 %, in the subcortical white matter – by 198 %, in the hippocampus – by 250 %, from the 23rd hour – in the caudate nucleus/putamen by 18 %. In the thalamus, no significant changes in the level of GFAP expression were observed. In the cortex and hippocampus of survived animals, 48 h after CLP, higher values of GFAP expression were observed comparing to the group of non-survived animals.

Conclusions. Under conditions of the experimental SAE, an early dynamic increase in the astroglial reactivity was observed in the cortex, hippocampus, white matter, and caudate nucleus/putamen of the brain with the most significant increase of indicators in the cortex and hippocampus, which potentially indicates relatively more vulnerable areas of the brain to damaging factors, as well as places of the most active intercellular interaction in the condition of systemic inflammation. Higher values of GFAP expression in the cortex and hippocampus of survived animals at 48 hours of the experiment, compared with indicators of non-survived group, indicate increased astroglial reactivity in these brain regions at the noted time period, accompanied by relatively more favorable clinical course of the disease.

 

Author Biographies

T. V. Shulyatnikova, Zaporizhzhia State Medical University, Ukraine

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

V. O. Tumaskyi, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor of the Department of Pathological Anatomy and Forensic Medicine, Vice-Rector for Research

References

  1. Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., Bellomo, R., Bernard, G. R., Chiche, J. D., Coopersmith, C. M., Hotchkiss, R. S., Levy, M. M., Marshall, J. C., Martin, G. S., Opal, S. M., Rubenfeld, G. D., van der Poll, T., Vincent, J. L., & Angus, D. C. (2016). The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315(8), 801-810. https://doi.org/10.1001/jama.2016.0287
  2. Mazeraud, A., Righy, C., Bouchereau, E., Benghanem, S., Bozza, F. A., & Sharshar, T. (2020). Septic-Associated Encephalopathy: a Comprehensive Review. Neurotherapeutics, 17(2), 392-403. https://doi.org/10.1007/s13311-020-00862-1
  3. Mazeraud, A., Pascal, Q., Verdonk, F., Heming, N., Chrétien, F., & Sharshar, T. (2016). Neuroanatomy and Physiology of Brain Dysfunction in Sepsis. Clinics in chest medicine, 37(2), 333-345. https://doi.org/10.1016/j.ccm.2016.01.013
  4. Chung, H. Y., Wickel, J., Brunkhorst, F. M., & Geis, C. (2020). Sepsis-Associated Encephalopathy: From Delirium to Dementia? Journal of clinical medicine, 9(3), 703. https://doi.org/10.3390/jcm9030703
  5. Verkhratsky, A., & Nedergaard, M. (2018). Physiology of astroglia. Physiological Reviews, 98, 239-389. https://doi.org/10.1152/physrev.00042.2016
  6. Zorec, R., Županc, T. A., & Verkhratsky, A. (2019). Astrogliopathology in the infectious insults of the brain. Neuroscience letters, 689, 56-62. https://doi.org/10.1016/j.neulet.2018.08.003
  7. Shulyatnikova, T., & Verkhratsky, A. (2020). Astroglia in Sepsis Associated Encephalopathy. Neurochemical research, 45(1), 83-99. https://doi.org/10.1007/s11064-019-02743-2
  8. Verkhratsky, A., Ho, M. S., Vardjan, N., Zorec, R., & Parpura, V. (2019). General Pathophysiology of Astroglia. Advances in experimental medicine and biology, 1175, 149-179. https://doi.org/10.1007/978-981-13-9913-8_7
  9. Zhang, S., Wu, M., Peng, C., Zhao, G., & Gu, R. (2017). GFAP expression in injured astrocytes in rats. Experimental and therapeutic medicine, 14(3), 1905-1908. https://doi.org/10.3892/etm.2017.4760
  10. Zhou, Y., Shao, A., Yao, Y., Tu, S., Deng, Y., & Zhang, J. (2020). Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury. Cell Communication And Signaling, 18(1). https://doi.org/10.1186/s12964-020-00549-2
  11. Shulyatnikova, T., & Shavrin, V. (2021). Mobilisation and redistribution of multivesicular bodies to the endfeet of reactive astrocytes in acute endogenous toxic encephalopathies. Brain research, 1751, 147174. https://doi.org/10.1016/j.brainres.2020.147174
  12. Oberheim, N. A., Goldman, S. A., & Nedergaard, M. (2012). Heterogeneity of astrocytic form and function. Methods in molecular biology, 814, 23-45. https://doi.org/10.1007/978-1-61779-452-0_3
  13. Batiuk, M. Y., Martirosyan, A., Wahis, J., de Vin, F., Marneffe, C., Kusserow, C., Koeppen, J., Viana, J. F., Oliveira, J. F., Voet, T., Ponting, C. P., Belgard, T. G., & Holt, M. G. (2020). Identification of region-specific astrocyte subtypes at single cell resolution. Nature communications, 11(1), 1220. https://doi.org/10.1038/s41467-019-14198-8
  14. Matias, I., Morgado, J., & Gomes, F. (2019). Astrocyte Heterogeneity: Impact to Brain Aging and Disease. Frontiers in aging neuroscience, 11, 59. https://doi.org/10.3389/fnagi.2019.00059
  15. Hol, E. M., & Pekny, M. (2015). Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Current opinion in cell biology, 32, 121-130. https://doi.org/10.1016/j.ceb.2015.02.004
  16. Chai, H., Diaz-Castro, B., Shigetomi, E., Monte, E., Octeau, J. C., Yu, X., Cohn, W., Rajendran, P. S., Vondriska, T. M., Whitelegge, J. P., Coppola, G., & Khakh, B. S. (2017). Neural Circuit-Specialized Astrocytes: Transcriptomic, Proteomic, Morphological, and Functional Evidence. Neuron, 95(3), 531-549.e9. https://doi.org/10.1016/j.neuron.2017.06.029
  17. Bondi, H., Bortolotto, V., Canonico, P. L., & Grilli, M. (2021). Complex and regional-specific changes in the morphological complexity of GFAP+ astrocytes in middle-aged mice. Neurobiology of aging, 100, 59-71. https://doi.org/10.1016/j.neurobiolaging.2020.12.018
  18. Yoon, H., Walters, G., Paulsen, A. R., & Scarisbrick, I. A. (2017). Astrocyte heterogeneity across the brain and spinal cord occurs developmentally, in adulthood and in response to demyelination. PloS one, 12(7), e0180697. https://doi.org/10.1371/journal.pone.0180697
  19. Shulyatnikova, T., & Shavrin, V. (2021). Regional-specific activation of phagocytosis in the rat brain in the conditions of sepsis-associated encephalopathy. Zaporozhye medical journal, 23(1), 111-119. https://10.14739/2310-1210.2021.1.224921

Downloads

Published

2021-12-01

How to Cite

1.
Shulyatnikova TV, Tumaskyi VO. Immunohistochemical analysis of GFAP expression in the experimental sepsis-associated encephalopathy. Pathologia [Internet]. 2021Dec.1 [cited 2026May25];18(3):295-302. Available from: https://pat.zsmu.edu.ua/article/view/240033

Issue

Section

Original research