Nestin, CD44, Ki-67, GS and AQP4 expression in the brain neurogenic niches of deceased patients with liver cirrhosis of different degree
Authors: Shulyatnikova T. V. , Tumanskiy V. O. 
Published: October 2023

The aim of the study. Immunohistochemical study of Nestin, CD44, Ki-67, GS, AQP4 expression in the subventricular zone of the lateral ventricle and hippocampus of deceased patients with liver cirrhosis depending on the age and Child–Pugh score.
Materials and methods. The brains of 90 deceased patients aged 65 ± 3 years with non-alcoholic liver cirrhosis (LC) Child–Pugh class A, B and C were studied, which comprised 3 groups: group “A” – 30 deceased patients with compensated LC; “B” – 30 deceased patients with subcompensated LC (“mild decompensation”); “C” – 30 deceased patients with decompensated LC. Control group included brains of 30 patients died from acute cardiovascular failure and did not have liver disease. Each group was divided into 2 subgroups: patients ≤59 y. o. and patients ≥60 y. o. Grade 1–4 hepatic encephalopathy was detected in 59 out of 90 (65.55 %) patients with LC. The immunohistochemical levels of Nestin, CD44, Ki-67, GS and AQP4 were evaluated in paraffin tissue sections of the subventricular zones (SVZ) of the anterior and lower horns of the brain lateral ventricles, as well as the subgranular zone (SGZ) of the dentate gyrus (DG) and other structures of hippocampus in standardized fields of view of the microscope Scope A1 Carl Zeiss (Germany) using Videotest-Morphology 5.2.0.158 software.
Results. In SVZ of control subgroups, Nestin+ astrocyte-like stem cells were localized mainly in subventricular glial nodules (SGN) and to a lesser extent in astrocytic ribbon. In brains of patients with compensated and subcompensated LC, there was increased Nestin expression compared to control (by 61.36 % and 208.74 %, respectively) due to increased numbers of Nestin+ cells in astrocytic ribbons. In the hippocampus of control and cirrhotic patients, Nestin expression was determined mainly in astrocyte-like cells of the fimbria-fornix, “glial plates” around the blood vessels entering the choroid plexus and subpial zone. In the SVZ of patients with subcompensated LC, the expressions of Nestin, CD44, and Ki-67 were maximally increased (by 208.74 %, 37.83 %, and 3 times, respectively), moreover, in the areas of periventricular reparative astrogliosis, in small foci of encephalolysis in the head of caudate nucleus, among GS+ and CD44+ astrocytes clusters of astrocyte-like Nestin+ and CD44+ cells were detected. In patients with decompensated LC, a significant decrease in Nestin and CD44 expression and absence of Ki-67 were observed in the SVZ, with a simultaneous maximum increase in the expression of GS and AQP4.
Conclusions. In the neurogenic niches of the lateral ventricles and hippocampus of patients with compensated and subcompensated LC, there are signs of activation of neural stem cells and niche astrocytes with increased expression of Nestin, CD44, and Ki-67, which reaches maximum in subcompensated LC. Clusters of astrocyte-like Nestin+ and CD44+ cells appear in foci of periventricular repair, which probably migrate from active adjacent subventricular niche. In the brains of the patients with decompensated LC and severe Grade 3–4 hepatic encephalopathy, deep astrocytic dysmetabolic dystrophy is associated with substantial decrease in the activity of subventricular stem niche and expected astrocytogenesis.