:: Volume 7, Issue 1 (Winter - 2019) ::
Shefaye Khatam 2019, 7(1): 77-90 Back to browse issues page
Hepatic Encephalopathy: Pathogenesis and Treatment Strategies
Shiler Khaledi , Shamseddin Ahmadi *
Department of Biological Science and Biotechnology, Faculty of Sciences, University of Kurdistan, Sanandaj, Iran , sh.ahmadi@uok.ac.ir
Abstract:   (52337 Views)
Introduction: Hepatic encephalopathy (HE) is a complicated brain disorder that has resulted from the liver failure. In HE, due to the inability of the liver in detoxification, the concentration of toxins, such as ammonia, will be increased in the blood and brain. To preserve neurons from the adverse effects of ammonia, astrocytes convert it to glutamine. The increase in glutamine, in turn, alter osmotic pressure and the volume of the interstitial fluid in the brain. On the other hand, the increase in ammonia level also excites immune cells in the brain and induces neuroinflammation. The high levels of ammonia and subsequent neuroinflammation alter neurotransmitter levels, which in turn induce cognitive dysfunctions, including learning and memory impairments as well as locomotion and coordination disorders. Glutamate and GABA and the downstream signaling cascades are the main molecular pathways that are affected in HE. Conclusion: According to the latest molecular data, it can be concluded that different signaling molecules downstream to the neurotransmitters receptors, such as Ca2+-dependent kinases including protein kinase C and calcium/calmodulin-dependent protein kinase II, mitogen-activated protein kinases and inflammatory cytokines, are proposed as the effective molecules in pathogenesis as well as potential targets for controlling and treatments of HE in the future. Considering the multidimensional appearance of HE, it can be proposed that a complex of treatment strategies, including the use of lowering ammonia level agents, effective antibiotics, anti-inflammatory drugs, and a balance in protein intake can effectively control the symptoms of HE.
Keywords: Hepatic Encephalopathy, Ammonia, Therapeutics, Protein Kinases
Full-Text [PDF 697 kb]   (18347 Downloads)    
Type of Study: Review --- Open Access, CC-BY-NC | Subject: Neurophysiopathology
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