Key astroglial markers in human liver cirrhosis of different degree: immunohistochemical study
The aim of the study – determining the immunohistochemical levels of the GFAP, GS and AQP4 in different regions of the human brain in the conditions of liver cirrhosis of different degree. Materials and methods. The study was performed on sectional material of 90 patients who suffered during life...
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| Format: | Article |
| Language: | English |
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Zaporozhye State Medical University
2022-11-01
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| Series: | Zaporožskij Medicinskij Žurnal |
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| Online Access: | http://zmj.zsmu.edu.ua/article/view/261327/262728 |
| _version_ | 1798015473664655360 |
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| author | T. V. Shulyatnikova V. O. Tumanskyi |
| author_facet | T. V. Shulyatnikova V. O. Tumanskyi |
| author_sort | T. V. Shulyatnikova |
| collection | DOAJ |
| description | The aim of the study – determining the immunohistochemical levels of the GFAP, GS and AQP4 in different regions of the human brain in the conditions of liver cirrhosis of different degree.
Materials and methods. The study was performed on sectional material of 90 patients who suffered during lifetime from liver non-alcoholic cirrhosis of classes A (n = 30, group “A”), B (n = 30, group “B”) and C (n = 30, group “C”) according to Child–Pugh classification, including 59 (65.55 %) cases with clinical symptoms of I–IV grade hepatic encephalopathy. Cortex, white matter, hippocampus, thalamus, striopallidum, cerebellum, were examined using immunohistochemical method for evaluation of GFAP, GS and AQP4 levels.
Results. GFAP expression gradually decreased from classes A to C of cirrhosis. The most expressed GFAP decline was found in class C in the cortex and thalamus (6.74- and 6.23-fold decrease). Contrary to GFAP, GS expression gradually increased along with aggravation of cirrhosis. The most prominent augmentation of GS was related in the cortex and thalamus in “C” group, respectively 4.34- and 4.26-fold increase. AQP4 levels also showed growing mode correlated with cirrhosis aggravation. The highest increase was found in the cortex and thalamus in “C” group (4.25- and 4.34-fold increase, respectively). Starting from class B, altered GFAP, GS, and AQP4 levels showed region-dependent relationships. GS and AQP4 were positively correlated in all 6 studied regions, while the inverse relationships were found between GFAP vs. GS and GFAP vs. AQP4 proteins.
Conclusions. As early as in class A of cirrhosis, dynamic molecular alterations are occurred in the brain astrocytes, indicating the progressive development of astroglial remodeling with a violation of its cytoskeleton and redistribution of molecular domains within cells. This phenomenon is region- and time-specific; its signs get stronger with time from class to class, becoming most pronounced in class C. Among studied brain regions, cortex and thalamus are characterized by the most pronounced protein changes. Starting from class B, the remarkable relationship is seen between molecular changes of both direct and inverse type. Simultaneously emerging links might indicate synergistic involvement of these molecules in astroglial remodeling in chronic hepatic encephalopathy. Alterations in the mentioned astroglial molecular complex can serve both as a diagnostic marker of reactive astrogliosis during liver cirrhosis and represent a target for novel therapeutic approaches regarding encephalopathy in cirrhotic patients. |
| first_indexed | 2024-04-11T15:35:05Z |
| format | Article |
| id | doaj.art-d60f9fa7e8cf4a808026c34d36154f32 |
| institution | Directory Open Access Journal |
| issn | 2306-4145 2310-1210 |
| language | English |
| last_indexed | 2024-04-11T15:35:05Z |
| publishDate | 2022-11-01 |
| publisher | Zaporozhye State Medical University |
| record_format | Article |
| series | Zaporožskij Medicinskij Žurnal |
| spelling | doaj.art-d60f9fa7e8cf4a808026c34d36154f322022-12-22T04:16:03ZengZaporozhye State Medical UniversityZaporožskij Medicinskij Žurnal2306-41452310-12102022-11-0124552953710.14739/2310-1210.2022.5.261327Key astroglial markers in human liver cirrhosis of different degree: immunohistochemical studyT. V. Shulyatnikova0https://orcid.org/0000-0002-0196-9935V. O. Tumanskyi1https://orcid.org/0000-0001-8267-2350Zaporizhzhia State Medical University, UkraineZaporizhzhia State Medical University, UkraineThe aim of the study – determining the immunohistochemical levels of the GFAP, GS and AQP4 in different regions of the human brain in the conditions of liver cirrhosis of different degree. Materials and methods. The study was performed on sectional material of 90 patients who suffered during lifetime from liver non-alcoholic cirrhosis of classes A (n = 30, group “A”), B (n = 30, group “B”) and C (n = 30, group “C”) according to Child–Pugh classification, including 59 (65.55 %) cases with clinical symptoms of I–IV grade hepatic encephalopathy. Cortex, white matter, hippocampus, thalamus, striopallidum, cerebellum, were examined using immunohistochemical method for evaluation of GFAP, GS and AQP4 levels. Results. GFAP expression gradually decreased from classes A to C of cirrhosis. The most expressed GFAP decline was found in class C in the cortex and thalamus (6.74- and 6.23-fold decrease). Contrary to GFAP, GS expression gradually increased along with aggravation of cirrhosis. The most prominent augmentation of GS was related in the cortex and thalamus in “C” group, respectively 4.34- and 4.26-fold increase. AQP4 levels also showed growing mode correlated with cirrhosis aggravation. The highest increase was found in the cortex and thalamus in “C” group (4.25- and 4.34-fold increase, respectively). Starting from class B, altered GFAP, GS, and AQP4 levels showed region-dependent relationships. GS and AQP4 were positively correlated in all 6 studied regions, while the inverse relationships were found between GFAP vs. GS and GFAP vs. AQP4 proteins. Conclusions. As early as in class A of cirrhosis, dynamic molecular alterations are occurred in the brain astrocytes, indicating the progressive development of astroglial remodeling with a violation of its cytoskeleton and redistribution of molecular domains within cells. This phenomenon is region- and time-specific; its signs get stronger with time from class to class, becoming most pronounced in class C. Among studied brain regions, cortex and thalamus are characterized by the most pronounced protein changes. Starting from class B, the remarkable relationship is seen between molecular changes of both direct and inverse type. Simultaneously emerging links might indicate synergistic involvement of these molecules in astroglial remodeling in chronic hepatic encephalopathy. Alterations in the mentioned astroglial molecular complex can serve both as a diagnostic marker of reactive astrogliosis during liver cirrhosis and represent a target for novel therapeutic approaches regarding encephalopathy in cirrhotic patients.http://zmj.zsmu.edu.ua/article/view/261327/262728liver cirrhosisastrogliareactivitygfapgsaqp4hepatic encephalopathyimmunohistochemistry |
| spellingShingle | T. V. Shulyatnikova V. O. Tumanskyi Key astroglial markers in human liver cirrhosis of different degree: immunohistochemical study Zaporožskij Medicinskij Žurnal liver cirrhosis astroglia reactivity gfap gs aqp4 hepatic encephalopathy immunohistochemistry |
| title | Key astroglial markers in human liver cirrhosis of different degree: immunohistochemical study |
| title_full | Key astroglial markers in human liver cirrhosis of different degree: immunohistochemical study |
| title_fullStr | Key astroglial markers in human liver cirrhosis of different degree: immunohistochemical study |
| title_full_unstemmed | Key astroglial markers in human liver cirrhosis of different degree: immunohistochemical study |
| title_short | Key astroglial markers in human liver cirrhosis of different degree: immunohistochemical study |
| title_sort | key astroglial markers in human liver cirrhosis of different degree immunohistochemical study |
| topic | liver cirrhosis astroglia reactivity gfap gs aqp4 hepatic encephalopathy immunohistochemistry |
| url | http://zmj.zsmu.edu.ua/article/view/261327/262728 |
| work_keys_str_mv | AT tvshulyatnikova keyastroglialmarkersinhumanlivercirrhosisofdifferentdegreeimmunohistochemicalstudy AT votumanskyi keyastroglialmarkersinhumanlivercirrhosisofdifferentdegreeimmunohistochemicalstudy |