Abstract
Hepatic encephalopathy (HE) encompasses a variety of neuropsychiatric symptoms, including anxiety and psychomotor dysfunction. Although HE is a frequent complication of liver cirrhosis, the neurobiological substrates responsible for its clinical manifestations are largely unclear. In the present study, male Wistar rats were bile duct-ligated (BDL), a procedure which induces liver cirrhosis, and on the 21st day after surgery tested in the elevated plus-maze (EPM) and in an open field for anxiety and locomotor activity measurements. Analysis of Fos protein immunoreactivity (Fos-ir) was used to better understand the neurobiological alterations present in BDL animals. Plasma levels of ammonia were quantified and histopathological analysis of the livers was performed. BDL rats showed a significant decrease in the percentage of entries and time spent in the open arms of the EPM, an anxiogenic effect. These animals also presented significant decreases in Fos-ir in the lateral septal nucleus and medial amygdalar nucleus. Their ammonia plasma levels were significantly higher when compared to the sham group and the diagnosis of cirrhosis was confirmed by histopathological analysis. These results indicate that the BDL model induces anxiogenic results, possibly related to changes in the activation of anxiety-mediating circuitries and to increases in ammonia plasma levels.
Highlights
Liver cirrhosis is a chronic disease, commonly caused by alcohol abuse or hepatitis C, which may be defined as the histological development of rege nerative nodules encircled by fibrous bands as a reaction to liver injury (Schuppan and Afdhal 2008)
The unpaired Student T-test indicated that the bile duct-ligated (BDL) group showed a significant decrease in the percentage of entries (T (9.19) = 11.76; P < 0.001) and time spent in the open arms of the elevated plus-maze (EPM) (T (16) = 2.99; P = 0.009)
The results of the present study showed that BDL animals exhibited a significant decrease in the percentage of entries and time spent in the open arms of the EPM, without significant alterations in motor activity
Summary
Liver cirrhosis is a chronic disease, commonly caused by alcohol abuse or hepatitis C, which may be defined as the histological development of rege nerative nodules encircled by fibrous bands as a reaction to liver injury (Schuppan and Afdhal 2008). The prevalence of liver cirrhosis is approximately 35 per 100,000 of the population overall, with an incidence of approximately 5 per 100,000 per year It is the 12th leading cause of hospitalizations and death in the US (Kim et al 2000). One of the main complications of liver cirrhosis is hepatic encephalopathy (HE) (Butterworth 2003, Garcia-Tsao 2001) This term has been used to identify a broad variety of neuropsychiatric abnormalities (i.e., anxiety and depression symptoms, altered sleep patterns and cognitive and psychomotor impairments), which can occur in cirrhotic patients, after exclusion of other neurological and/or metabolic causes (Butterworth 2003, Sunmonu et al 2012). When HE is severe, patients may develop variable degrees of confusion and even coma (Ferenci et al 1998)
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