Aspectos comportamentais associados às alterações patológicas, inflamatórias e neuroquímicas na encefalopatia hepática experimental

Abstract

Hepatic encephalopathy (HE) is a neurological complication observed in hepatic failure. HE patients may present neuropsychiatric, neuromuscular, and behavioral disorders, which may impair quality of life and work capability. Currently, the only definitive treatment for hepatic failure is transplantation, which highlights the need for complete understanding of the pathophysiology and mechanisms involved in the disease, in order to establish new therapeutic targets and supportive measures until transplantation is available. Experimental models of HE in rodents have been widely used. It is believed that these models provide relevant information for understanding the mechanisms involved in the pathogenesis of the disease, as well as the development of new therapeutic targets. Studies evaluating neurological sequelae after the development of hepatic encephalopathy as well as its association with tissue data, inflammatory and neurochemical profiles in later stages of the disease are scarce. Using C57BL/6 female mice, between eight and twelve weeks age, we investigated behavioral and pathological changes association with inflammatory and neuroprotective responses during HE that follows hepatic failure induced by intraperitoneal injection of thioacetamide (TAA). Mice were divided into TAA and control groups, the latter being submitted to intraperitoneal injection of saline. TAA animals presented liver damage associated with increased activity of neutrophils and macrophages. In addition, induced animals demonstrated in the applied tests, anxiety-like and depression-like behavior and morphological changes of astrocytes and microglia. This same group showed a significant reduction in expression of proinflammatory cytokines interferon- (IFN-) and interleukin-6 (IL-6) in the hippocampus and the brain-derived neurotrophic factor (BNDF) in the cerebral cortex when compared to the control animals. Our results suggest that inflammatory and neuroprotective responses disorders are associated with behavioral deficits in murine hepatic encephalopathy.