The aim of our study was to investigate the behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy in rats. Male Wistar rats were divided among (i) control, saline-treated, and (ii) thioacetamide-treated groups (TAA(300) (300 mg/kg body mass); TAA(600) (600 mg/kg); and TAA(900) (900 mg/kg)). The daily dose of thioacetamide (300 mg/kg) was administered intraperitoneally once (TAA(300)), twice (TAA(600)), or 3 times (TAA(900)), on subsequent days. Behavioral manifestations were determined at 0, 2, 4, 6, and 24 h, while electroencephalographic changes were recorded 22-24 h after the last dose. General motor activity and exploratory behavior, as well as head shake, auditory startle reflex, placement, and equlibrium tests were diminished in the TAA(600) and TAA(900) groups compared with the control, and were absent in the TAA(900) group 24 h after treatment. Corneal, withdrawal, grasping, and righting reflexes were significantly diminished in the TAA(900) group compared with the control. Mean electroencephalographic power spectra density was significantly higher in TAA(300) and TAA(600) and lower in the TAA(900) group by comparison with the control. Only a score of 3 (mean dominant frequency ≤ 7.3 Hz and δ relative power ≥ 45%) was observed in the TAA(900) group. Thioacetamide induces encephalopathy in rats in a dose-dependent manner. A dose of 900 mg/kg TAA may be used as a suitable model of all stages of hepatic encephalopathy.

(HE). This study evaluated the effects of finasteride, inhibitor of neurosteroid synthesis, on motor, EEG, and cellular changes in rat brain in thioacetamide-induced HE. Male Wistar rats were divided into the following groups: 1) control; 2) thioacetamide-treated group, TAA (300 mg·kg Ϫ1 ·day Ϫ1 ); 3) finasteride-treated group, FIN (50 mg·kg Ϫ1 ·day Ϫ1 ); and 4) group treated with FIN and TAA (FIN ϩ TAA). Daily doses of TAA and FIN were administered in three subsequent days intraperitoneally, and in the FIN ϩ TAA group FIN was administered 2 h before every dose of TAA. Motor and reflex activity was determined at 0, 2, 4, 6, and 24 h, whereas EEG activity was registered about 24 h after treatment. The expressions of neuronal (NeuN), astrocytic [glial fibrilary acidic protein (GFAP)], microglial (Iba1), and oligodendrocyte (myelin oligodendrocyte glycoprotein) marker were determined 24 h after treatment. While TAA decreased all tests, FIN pretreatment (FIN ϩ TAA) significantly improved equilibrium, placement test, auditory startle, head shake reflex, motor activity, and exploratory behavior vs. the TAA group. Vital reflexes (withdrawal, grasping, righting and corneal reflex) together with mean EEG voltage were significantly higher (P Ͻ 0.01) in the FIN ϩ TAA vs. the TAA group. Hippocampal NeuN expression was significantly lower in TAA vs. control (P Ͻ 0.05). Cortical Iba1 expression was significantly higher in experimental groups vs. control (P Ͻ 0.05), whereas hippocampal GFAP expression was increased in TAA and decreased in the FIN ϩ TAA group vs. control (P Ͻ 0.05). Finasteride improves motor and EEG changes in TAA-induced HE and completely prevents the development of hepatic coma. motor tests; electroencephalography; cellular markers HEPATIC ENCEPHALOPATHY (HE) represents a clinical syndrome characterized by neurological and psychiatric disturbances that develop as a result of acute or chronic liver failure (21). Various mechanisms are involved in the pathogenesis of HE, including changes in neurotransmission (17), oxidative stress, bioenergetic failure, mitochondrial permeability transition (49), inflammatory response, and immune dysfunction (14, 52), due to accumulation of various toxins in the organism, principally ammonia (4).Changes in glutamatergic and GABAergic transmission have an important role in the development of HE (13, 16). Both acute and chronic liver failure were found to be associated with increased GABAergic activity due to increased neurosteroid synthesis. Neurosteroids are steroid compounds, synthesized in mitochondria of glial cells and neurons from cholestrol (2). Cholesterol is taken up into mitochondria via the activation of translocator protein (TSPO), a multimeric complex that spans both outer and inner mitochondrial membrane. Ammonia and manganese, toxins accumulated in HE, and proinflammatory cytokines upregulate components of TSPO and increase cholesterol uptake into the mitochondrion (2, 4). Cholesterol serves as a substrate for increased synthesis of neurosteroids, including all...

SummaryBackgroundWest Nile virus neuroinvasive disease (WNND) occurs in less than 1% of infected people. Leukocytosis with lymphocytopenia, mild anaemia, thrombocytopenia, elevated liver and muscle enzymes and hyponatremia are occasionally present in patients with WNND. Cerebrospinal fluid (CSF) findings resemble other viral neuroinfections. The purpose of this study is to pre sent some of the most important laboratory findings of our patients with WNND and to evaluate their correlation with fatal outcome.MethodsThe study included 161 patients with WNND. Their blood and CSF samples were cytobiochemically analysed and the obtained variables were then tested for predictive significance of the disease outcome, or used for differentiation between two clinical syndromes (encephalitis vs meningitis).ResultsWest Nile encephalitis was present in 127 (78.9%) patients and West Nile meningitis was diagnosed in 34 (21.1%) cases. Leukocytosis was found in 45.9% patients. CRP level higher than 100 mg/L was registered only in those with encephalitis (p=0.020). CSF leukocyte count was 146±171 per microlitre, with slight lymphocytic predominance (mean 52%). Hypoglycorrhachia was registered in 9.3% of our patients with WNND. Twenty-eight (17.4%) patients died and all of them had encephalitis. Independent predictors of fatal outcome in WNND were serum CRP > 100 mg/L (p=0.011) and CSF proteins > 1 g/L (p=0.002).ConclusionsWNND usually affects older males. Prolonged neutrophilic predominance in CSF can occasionally be present, as well as hypoglycorrhachia. Patients with encephalitis, high serum CRP and high CSF protein level have a higher risk of fatal outcome.

Finasteride (FIN) inhibits neurosteroid synthesis and potentially improves the course of hepatic encephalopathy (HE). This study aimed to investigate the effects of FIN on brain oxidative stress and acetylcholinesterase (AchE) activity in acute thioacetamide-induced HE in rats. Male Wistar rats were divided into groups: 1. control; 2. thioacetamide-treated group (TAA; 900 mg/kg); 3. finasteride-treated group (FIN; 150 mg/kg); 4. group treated with FIN and TAA (FIN+TAA). Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered intraperitoneally during three days and in FIN+TAA group FIN was administered 2h before every dose of TAA. FIN pretreatment prevented TAA-induced rise in malondialdehyde level in the cortex due to restoration of catalase activity and increased expression of superoxide dismutase 1 (SOD1) and induced an increase in malondialdehyde level in the thalamus due to reduction of glutathione peroxidase (GPx) and glutathione reductase (GR) activity. Although FIN pretreatment did not affect malondialdehyde level in hippocampus and caudate nucleus, hippocampal SOD1 expression was higher (p<0.05) and GR activity lower in FIN+TAA vs. TAA group (p<0.05). GPx activity was lower in caudate nucleus in FIN+TAA vs. TAA group (p<0.01). FIN pretreatment prevented TAA-induced rise in AchE activity in the thalamus and caudate nucleus and AchE activity correlates inversely in the thalamus (p<0.05) and positively in caudate nucleus (p<0.01) with malondialdehyde level. FIN has regionally selective effects on oxidative stress and AchE activity in the brain in acute TAA-induced HE in rats. The prooxidant role of FIN in the thalamus may be causally linked with inhibition of AchE.

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