Time dependent alteration of locomotor behavior in rat with acute liver failure induced cerebellar neuroinflammation and neuro-astroglial damage

Hepatic encephalopathy (HE) is a neurophysiological syndrome secondary to acute or chronic liver failure. Studies showed that HE patients exhibit a deficit in motor coordination, which may result from cerebellar functional impairment. The aim of this study is to assess the time-dependent alteration...

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Veröffentlicht in:Journal of chemical neuroanatomy 2022-01, Vol.119, p.102055, Article 102055
Hauptverfasser: El Khiat, Abdelaati, El Hiba, Omar, Tamegart, Lahcen, Rais, Hanane, Fdil, Naima, Sellami, Souad, El Mokhtar, Mohamed Ait, Gamrani, Halima
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Sprache:eng
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Zusammenfassung:Hepatic encephalopathy (HE) is a neurophysiological syndrome secondary to acute or chronic liver failure. Studies showed that HE patients exhibit a deficit in motor coordination, which may result from cerebellar functional impairment. The aim of this study is to assess the time-dependent alteration of locomotor behavior and the glial and neuronal alteration 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 test and the Rotarod test for assessing the locomotor activity and coordination. 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 parallel to increased COX-2 immunoreactivity together with astrocytic morphology and density changes. Likewise, in substantia nigra pars compacta, TH levels were reduced. 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. •Acute liver failure in rat elicits progressive time-dependant loss of motor coordination.•Acute hepatic encephalopathy in rat is associated to deficient dopaminergic innervations.•Impaired motor coordination may result from morphological astroglial modifications leading to deep functional disruptions.•Presence of cerebellar neuroinflammation correlated to neuronal death of Purkinje cells.
ISSN:0891-0618
1873-6300
DOI:10.1016/j.jchemneu.2021.102055