Elsherbini Dalia Mahmoud Abdelmonem, Ghoneim Fatma M, El-Mancy Eman Mohammed, Ebrahim Hasnaa Ali, El-Sherbiny Mohamed, El-Shafey Mohamed, Al-Serwi Rasha Hamed, Elsherbiny Nehal M
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka, Saudi Arabia.
Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Front Cell Neurosci. 2022 Aug 17;16:896172. doi: 10.3389/fncel.2022.896172. eCollection 2022.
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.
肝性脑病（HE）是一种神经功能紊乱，表现为慢性和急性肝衰竭（ALF）的后遗症。ALF的一个潜在致命后果是脑水肿并伴有星形胶质细胞肿大。本研究旨在概述星形胶质细胞在急性HE中的作用，并阐明驱动这一作用的最关键机制。将大鼠分为两组。第1组为对照组，给予赋形剂。第2组为TAA组，接受TAA（300mg/kg）治疗3天。测定血清AST、ALT和氨水平。对肝脏和大脑皮质切片进行苏木精和伊红染色。此外，还进行了皮质GFAP、TNFα、Kir4.1和AQP4的mRNA表达和免疫组织化学染色。TAA组的皮质切片显示神经毡空泡化和星形胶质细胞肿大，并伴有局灶性胶质增生。GFAP、TNFα和AQP4显示mRNA表达增加、免疫反应阳性，且与脑含水量呈正相关。相反，Kir 4.1显示mRNA表达和免疫反应性降低，且与脑含水量呈负相关。总之，我们的研究结果揭示了与HE相关的脑水肿中TNFα、Kir 4.1、GFAP和AQP4水平的改变。与AQP4和GFAP相比，观察到Kir 4.1和TNFα的失调更为显著。
