Immunohistochemical analysis of the glial fibrillary acidic protein expression in the experimental acute hepatic encephalopathy

Authors

Keywords:

acute hepatic encephalopathy, astroglial reactivity, GFAP

Abstract

Background. Pathophysiology of acute hepatic encephalopathy (AHE) is complex and fine links of its development are still to be recognized. It is believed that AHE mechanisms are commonly focused on the ammonia neurotoxicity associated with neuroinflammation, neurotransmitter disbalance and severe astrocytic swelling leads to generalized brain edema. Astroglia, principal homeostatic cell population in the brain are suggested to be the primary target for hyperammonemia in this condition. Being highly region- and context-dependently heterogenic, its response to various pathological actions is also supposed to be highly diverse. The objective determining the immunohistochemical features of glial fibrillary acidic protein (GFAP) expression in different rat brain regions in the conditions of experimental acute hepatic encephalopathy. Methods. The study was conducted in Wistar rats: 5 sham (control) animals and 10 rats with acetaminophen induced liver failure model (AILF). The immunohistochemical study of GFAP expression in the sensorimotor cortex, white matter, hippocampus, thalamus, caudate nucleus/putamen region was carried out in the period of 12-24 h after injection. Results. Beginning from the 6th hour after injection all animals of AILF-group showed the progressive increase in clinical signs of acute brain disfunction finished in 6 rats by comatose state up to 24 h; they constituted subgroup AILF-B, “non-survived”. Four animals survived until the end of the experiment, 24 h (subgroup AILF-A “survived”). In the AILF-B group, starting from 16 to 24 hours after the AILF-procedure, a significant (relative to control) regionally-specific dynamic decrease in the level of GFAP expression was observed in the brain: in the subcortical white matter by 125.65%, in the thalamus by 526.66%, in the caudate nucleus/putamen by 103.12%, in the hippocampus by 176.31%, from 18th hour in the cortex, by 537.5% with the most substantive reduction in the cortex and thalamus: by 6.47 and 6.26 times, respectively. Conclusion. In the conditions of experimental AILF, there is early dynamic decrease in astroglial reactivity in the cortex, thalamus, hippocampus, white matter and caudate nucleus/putamen region. The most significant decrease in GFAP indices in the cortex and thalamus indicates these areas as more vulnerable to systemic aggressive factors and more susceptible to toxic and metabolic load in conditions of acute liver failure, and on the other hand, emphasizes relatively more pronounced sensitivity and reactivity of local astroglia to the action of damaging substances in this state and at this time period of the pathology development. The dynamic decrease in the level of GFAP in the rat brain, associated with the same dynamic deterioration in the state of animals, indicates the importance of such pathological astroglial remodeling in the mechanisms of AHE development in rats.

References

  1. Shulyatnikova T, Shavrin V. Modern view on hepatic encephalopathy: basic terms and concepts of pathogenesis. Pathologia. 2017;14(3):371-380. doi: 10.14739/2310-1237.2017.3.118773
  2. Ferenci P. Hepatic encephalopathy. Gastro-enterol Rep (Oxf). 2017 May;5(2):138-147. doi: 10.1093/gastro/gox013. Epub 2017 Apr 18. PMID: 28533911; PMCID: PMC5421503.
  3. Jayakumar AR, Norenberg MD. Hyperam-monemia in Hepatic Encephalopathy. J Clin Exp Hepatol. 2018 Sep;8(3):272-280. doi: 10.1016/j.jceh.2018.06.007. Epub 2018 Jun 20. PMID: 30302044; PMCID: PMC6175739.
  4. Dasarathy S, Mookerjee RP, Rackayova V, Rangroo Thrane V, Vairappan B, Ott P, Rose CF. Ammonia toxicity: from head to toe? Metab Brain Dis. 2017 Apr;32(2):529-538. doi: 10.1007/s11011-016-9938-3. Epub 2016 Dec 24. PMID: 28012068.
  5. Ochoa-Sanchez R, Tamnanloo F, Rose CF. Hepatic Encephalopathy: From Metabolic to Neurodegenerative. NERE. 2021;46(10):2612–2625. https://doi.org/10.1007/s11064-021-03372-4
  6. Butterworth RF. The concept of "the in-flamed brain" in acute liver failure: mechanisms and new therapeutic opportunities. Metab Brain Dis. 2016 Dec;31(6):1283-1287. doi: 10.1007/s11011-015-9747-0. Epub 2015 Oct 20. PMID: 26481639.
  7. Liotta EM, Kimberly WT. Cerebral edema and liver disease: Classic perspectives and contem-porary hypotheses on mechanism. Neurosci Lett. 2020 Mar 16;721:134818. doi: 10.1016/j.neulet.2020.134818. Epub 2020 Feb 5. PMID: 32035166; PMCID: PMC7773170.
  8. Agarwal AN, Mais DD. Sensitivity and Specificity of Alzheimer Type II Astrocytes in He-patic Encephalopathy. Arch Pathol Lab Med. 2019 Oct;143(10):1256-1258. doi: 10.5858/arpa.2018-0455-OA. Epub 2019 May 7. PMID: 31063011.
  9. Verkhratsky A, Ho MS, Vardjan N, Zorec R, Parpura V. General Pathophysiology of Astroglia. Advances in Experimental Medicine and Biology. 2019;1175:149-179. doi: 10.1007/978-981-13-9913-8_7. PMID: 31583588; PMCID: PMC7188602.
  10. Li D, Liu X, Liu T, Liu H, Tong L, Jia S, Wang YF. Neurochemical regulation of the expres-sion and function of glial fibrillary acidic protein in astrocytes. Glia. 2020 May;68(5):878-897. doi: 10.1002/glia.23734. Epub 2019 Oct 18. PMID: 31626364.
  11. Jaeger V, DeMorrow S, McMillin M. The Direct Contribution of Astrocytes and Microglia to the Pathogenesis of Hepatic Encephalopathy. J Clin Transl Hepatol. 2019 Dec 28;7(4):352-361. doi: 10.14218/JCTH.2019.00025. Epub 2019 Nov 13. PMID: 31915605; PMCID: PMC6943208.
  12. Batiuk M, Martirosyan A, Wahis J, de Vin F, Marneffe C, Kusserow C et al. Identification of region-specific astrocyte subtypes at single cell reso-lution. Nature Communications. 2020;11(1). doi: 10.1038/s41467-019-14198-8
  13. Shulyatnikova TV. Immunohistochemical analysis of microglial changes in the experimental acute hepatic encephalopathy. Pathologia. 2021;18(1):33-38. doi: 10.14739/2310-1237.2021.1.227642.
  14. Mitchell RA, Rathi S, Dahiya M, Zhu J, Hussaini T, Yoshida EM. Public awareness of acet-aminophen and risks of drug induced liver injury: Results of a large outpatient clinic survey. PLoS One. 2020 Mar 4;15(3):e0229070. doi: 10.1371/journal.pone.0229070. PMID: 32130228; PMCID: PMC7055817.
  15. McGill MR, Williams CD, Xie Y, Rama-chandran A, Jaeschke H. Acetaminophen-induced liver injury in rats and mice: comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. Toxicol Appl Pharmacol. 2012 Nov 1;264(3):387-94. doi: 10.1016/j.taap.2012.08.015. Epub 2012 Aug 23. PMID: 22980195; PMCID: PMC3478469.
  16. Mossanen JC, Tacke F. Acetaminophen-induced acute liver injury in mice. Lab Anim. 2015 Apr;49(1 Suppl):30-6. doi: 10.1177/0023677215570992. PMID: 25835736.
  17. Shulyatnikova T, Shavrin V. Mobilisation and redistribution of multivesicular bodies to the endfeet of reactive astrocytes in acute endogenous toxic encephalopathies. Brain Res. 2021 Jan 15;1751:147174. doi: 10.1016/j.brainres.2020.147174. Epub 2020 Oct 24. PMID: 33172595.
  18. Jayakumar AR, Rama Rao KV, Norenberg MD. Neuroinflammation in hepatic encephalopathy: mechanistic aspects. J Clin Exp Hepatol. 2015 Mar;5(Suppl 1):S21-8. doi: 10.1016/j.jceh.2014.07.006. Epub 2014 Aug 5. PMID: 26041953; PMCID: PMC4442850.
  19. Shulyatnikova T, Shavrin V. Regional-specific activation of phagocytosis in the rat brain in the conditions of sepsis-associated encephalopathy. Zaporozhye medical journal. 2021;23(1):111-119. doi: 10.14739/2310-1210.2021.1.224921.
  20. Thumburu KK, Dhiman RK, Vasishta RK, Chakraborti A, Butterworth RF, Beauchesne E, Desjardins P, Goyal S, Sharma N, Duseja A, Chawla Y. Expression of astrocytic genes coding for proteins implicated in neural excitation and brain edema is altered after acute liver failure. J Neurochem. 2014 Mar;128(5):617-27. doi: 10.1111/jnc.12511. Epub 2013 Nov 14. PMID: 24164438.
  21. Lachmann V, Görg B, Bidmon HJ, Keitel V, Häussinger D. Precipitants of hepatic encephalo-pathy induce rapid astrocyte swelling in an oxidative stress dependent manner. Arch Biochem Biophys. 2013 Aug 15;536(2):143-51. doi: 10.1016/j.abb.2013.05.004. Epub 2013 May 24. PMID: 23707757.
  22. Daverey A, Agrawal SK. Curcumin allevi-ates oxidative stress and mitochondrial dysfunction in astrocytes. Neuroscience. 2016 Oct 1;333:92-103. doi: 10.1016/j.neuroscience.2016.07.012. Epub 2016 Jul 14. PMID: 27423629.

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Published

2023-06-26

How to Cite

Shulyatnikova , T., & Tumanskiy , V. (2023). Immunohistochemical analysis of the glial fibrillary acidic protein expression in the experimental acute hepatic encephalopathy. Морфологія / Morphologia / Morfologìâ, 15(4), 96–105. Retrieved from https://morphology.dma.edu.ua/article/view/282865

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Vol. 15 No. 4 (2021)

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