Behavioral, Neurochemical and Brain Oscillation Abnormalities in an Experimental Model of Acute Liver Failure

•Subtotal hepatectomy impaired electrophysiological parameters.•Acute liver failure decreases locomotor activity and increases a lethality rate.•Acute liver failure induces glutamatergic excitotoxicity.•Here, we present an effective, reproducible and non-expensive model to study ALF. Hepatic encepha...

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Bibliographic Details
Published in:Neuroscience 2019-03, Vol.401, p.117-129
Main Authors: Cittolin-Santos, G.F., Guazzelli, P.A., Nonose, Y., Almeida, R.F., Fontella, F.U., Pasquetti, M.V., Ferreira-Lima, F.J., Lazzaroto, G., Berlezi, R.M., Osvaldt, A.B., Calcagnotto, M.E., de Assis, A.M., Souza, D.O.
Format: Article
Language:English
Subjects:
acute liver failure
behavior
brain dysfunction
glutamatergic system
hepatic encephalopathy
neurochemical oscillation
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Summary:•Subtotal hepatectomy impaired electrophysiological parameters.•Acute liver failure decreases locomotor activity and increases a lethality rate.•Acute liver failure induces glutamatergic excitotoxicity.•Here, we present an effective, reproducible and non-expensive model to study ALF. Hepatic encephalopathy (HE) represents a brain dysfunction caused by both acute and chronic liver failures, and its severity deeply affects the prognosis of patients with impaired liver function. In its pathophysiology, ammonia levels and glutamatergic system hyperactivity seem to play a pivotal role in the disruption of brain homeostasis. Here, we investigate important outcomes involved in behavioral performance, electroencephalographic patterns, and neurochemical parameters to better characterize the well-accepted animal model of acute liver failure (ALF) induced by subtotal hepatectomy (92% removal of tissue) that produces ALF. This study was divided into three cohorts: (1) rats clinically monitored after hepatectomy every 6 h for 96 h or until death; (2) rats tested in an open-field task (OFT) before and after surgery and had blood, cerebrospinal fluid, and brain tissue collected after the last OFT; and (3) rats that had continuous EEGs recorded before and after surgery for 3 days. The hepatectomized rats presented significant motor behavioral changes accompanied by important abnormalities in classical blood laboratory parameters of ALF, and EEG features suggestive of HE and deep disturbances in the brain glutamatergic system. Using an animal model of ALF induced via subtotal hepatectomy, this work provides a comprehensive and reliable experimental model that increases the opportunity for studying the effects of new treatment strategies to be explored in an unprecedented way. It also presents insights into the pathophysiology of HE in a reproducible model of ALF, which correlates important neurochemical and EEG aspects of the syndrome.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2018.12.032