Differential regional responsiveness of astroglia in mild hepatic encephalopathy: An Immunohistochemical approach in bile duct ligated rat

• During episodes of hepatic encephalopathy (HE) secondary to chronic liver failure, different brain neuronal systems undergo a functional alterations resulting from different peripheral dysfunctions.
• The glial system is highly involved in the regulation of the neuronal system especially astroglia known by manifesting features of a primary gliopathy named Alzheimer type II astrocytosis.
• Our data showed evidence of divergent altered glial cytoskeleton protein (glial fibrillary acidic protein: GFAP) in the brain cortex, dorsal striatum, hippocampus and midbrain substantia nigra compacta, and ventral tegmental area.
• Altered glial markers may reflect a profound altered function of these cells and consequently the environing neuronal systems, especially in the same brain regions, and can be taken into consideration for understanding the pathomechanisms of hepatic encephalopathy.

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. However, the pathomechanisms of the disease remains obscure. Neuropathological studies have demonstrated a primary gliopathy in humans as well as in animal models of chronic and acute liver failure. Here, we have investigated in an animal model of mild HE: the bile duct ligated rat (BDL) at the cirrhotic stage (4 weeks after surgery), the expression of the key marker of mature astrocytes; the glial fibrillary acidic protein (GFAP) in different brain areas such as: Substantia nigra pars compacta (SNc), Ventral tegmental area (VTA), hippocampus, dorsal striatum and brain cortex by means of immunohistochemistry. The immunohistochemical study showed, in BDL compared to the operated controls (shams), a diminished astrocyte reactivity corresponding to a loss of GFAP expression within SNc, VTA, hippocampus and dorsal striatum (p < 0.05),whereas in the brain cortex astrocytes appeared strongly immunoreactive with increased GFAP expression (p < 0.05) as compared to shams. Our finding demonstrated differential astroglial responses which depend to the specificity of the area investigated and its particular neuronal neighboring environment, and could have possible outcomes on the diverse neuronal functions especially those observed during the different episodes of hepatic encephalopathy.