P14 Altered Locomotor Behavior Associated With Purkinje Cells and Astrocytes Dysfunctions in Rat With Acute Hepatic Encephalopathy Involving the Oxidative Stress and Neuroinflammation

Abstract

Background: Hepatic encephalopathy (HE) is a wide range of neuropsychiatric abnormalities caused by acute or chronic liver failure. Studies showed that HE patients exhibit a deficit in motor coordination, which may result from cerebellar dysfunction. Methods: The aims of this study were to assess the time-dependent alteration of locomotor behavior and the glial and neuronal alterations in rat with acute HE induced chemically. The study was carried out in male Sprague-Dawley rats with thioacetamide (TAA) induced acute liver failure at different stages; 12 h, 24 h and 36 h. Hepatic and renal functions were assessed via various biochemical and histopathological examinations, while the cerebellum and the midbrain were examined using histology and immunohistochemistry for tyrosine hydroxylase (TH), cyclooxygenase-2 (COX-2) and glial fibrillary acidic protein (GFAP). We used as well, the open field and the Rotarod tests to assess locomotor activity and motor coordination. Results: Our data showed a progressive loss of liver function and a progressive alteration in locomotor behavior and motor coordination in acute HE rats. In the cerebellum, we noted an increase in the degeneration of cerebellar Purkinje neurons (Figure 1) parallel to increased COX-2 immunoreactivity together with astrocytic morphology and density changes. Likewise, in substantia nigra pars compacta, TH levels were reduced. Conclusions: We showed through the current study, a progressive deterioration in locomotor behavior in acute HE rats, as a result of Purkinje neurons death and a deficient dopaminergic neurotransmission, together with the morpho-functional astroglial modifications involving the oxidative stress and neuroinflammation.Figure 1.: Histogram of quantification of % degenerated Purkinje cells vs. to normal in the different groups: CTR, TAA12h, TAA24h and TAA36h. *p <0.05, **p <0.01, ***p <0.001 vs CTR. ##p <0.01 vs, ###p <0.001 vs TAA12h. μμμ, p <0.001 vs TAA24h.