Astrocytes profiling in acute hepatic encephalopathy: Possible enrolling of glial fibrillary acidic protein, tumor necrosis factor-alpha, inwardly rectifying potassium channel (Kir 4.1) and aquaporin-4 in rat cerebral cortex

Dalia Mahmoud Abdelmonem Elsherbini; Fatma M Ghoneim; Eman Mohammed El-Mancy; Hasnaa Ali Ebrahim; Mohamed El-Sherbiny; Mohamed El-Shafey; Rasha Hamed Al-Serwi; Nehal M Elsherbiny

doi:10.3389/fncel.2022.896172

Astrocytes profiling in acute hepatic encephalopathy: Possible enrolling of glial fibrillary acidic protein, tumor necrosis factor-alpha, inwardly rectifying potassium channel (Kir 4.1) and aquaporin-4 in rat cerebral cortex

Front Cell Neurosci. 2022 Aug 17:16:896172. doi: 10.3389/fncel.2022.896172. eCollection 2022.

Authors

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia.
² Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
³ Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁴ Deanship of Common First Year, Jouf University, Sakaka, Saudi Arabia.
⁵ Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo, Egypt.
⁶ Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia.
⁷ Department of Physiological Sciences, Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia.
⁸ Department of Basic Dental Sciences, College of Dentistry, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
⁹ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
¹⁰ Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

Abstract

Hepatic encephalopathy (HE) is a neurological disarray manifested as a sequel to chronic and acute liver failure (ALF). A potentially fatal consequence of ALF is brain edema with concomitant astrocyte enlargement. This study aims to outline the role of astrocytes in acute HE and shed light on the most critical mechanisms driving this role. Rats were allocated into two groups. Group 1, the control group, received the vehicle. Group 2, the TAA group, received TAA (300 mg/kg) for 3 days. Serum AST, ALT, and ammonia were determined. Liver and cerebral cortical sections were processed for hematoxylin and eosin staining. Additionally, mRNA expression and immunohistochemical staining of cortical GFAP, TNFα, Kir4.1, and AQP4 were performed. Cortical sections from the TAA group demonstrated neuropil vacuolation and astrocytes enlargement with focal gliosis. GFAP, TNFα, and AQP4 revealed increased mRNA expression, positive immunoreactivity, and a positive correlation to brain water content. In contrast, Kir 4.1 showed decreased mRNA expression and immunoreactivity and a negative correlation to brain water content. In conclusion, our findings revealed altered levels of TNFα, Kir 4.1, GFAP, and AQP4 in HE-associated brain edema. A more significant dysregulation of Kir 4.1 and TNFα was observed compared to AQP4 and GFAP.

Keywords: GFAP; TNFα; aquaporin-4; brain edema; inwardly rectifying potassium channel.