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Influence of Liver Pathology on Markers of Postmortem Brain Tissue Quality

Authors

  • Donna Sheedy,

    1. From the Discipline of Pathology (DS, MS, JS, CGH, JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Schizophrenia Research Institute (JS), Sydney, NSW, Australia; and Discipline of Medicine (JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
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  • Meichien Say,

    1. From the Discipline of Pathology (DS, MS, JS, CGH, JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Schizophrenia Research Institute (JS), Sydney, NSW, Australia; and Discipline of Medicine (JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
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  • Julia Stevens,

    1. From the Discipline of Pathology (DS, MS, JS, CGH, JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Schizophrenia Research Institute (JS), Sydney, NSW, Australia; and Discipline of Medicine (JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
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  • Clive G. Harper,

    1. From the Discipline of Pathology (DS, MS, JS, CGH, JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Schizophrenia Research Institute (JS), Sydney, NSW, Australia; and Discipline of Medicine (JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
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  • Jillian J. Kril

    1. From the Discipline of Pathology (DS, MS, JS, CGH, JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; Schizophrenia Research Institute (JS), Sydney, NSW, Australia; and Discipline of Medicine (JJK), Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
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Reprint requests: Jillian J. Kril, PhD, Discipline of Pathology, The University of Sydney, Sydney, NSW 2006, Australia; Tel.: +61-2-9036 7118; Fax +61-2-9351 3429; E-mail:jillian.kril@sydney.edu.au

Abstract

Background:  Postmortem brain tissue provides an important resource to investigate various brain disorders, including those resulting from the effects of alcohol abuse. Unlike the traditionally recognized confounders to tissue quality (e.g., coma, hypoxia), our understanding of the effects of liver disease is incomplete. The aim of this study was to determine the effects of liver pathology, and in particular cirrhosis resulting in hepatic encephalopathy (HE), on 2 postmortem brain tissue quality markers, brain pH and RNA integrity.

Methods:  We measured tissue quality markers in a cohort of alcohol abuse and control cases collected by the NSW Tissue Resource Centre. Cerebellar tissue was used to evaluate both brain pH and RNA quality (as indicated by the RNA integrity number: RIN). A histological assessment was performed on each case to exclude coexisting pathologies (e.g., cerebrovascular disease, hypoxic encephalopathy, neurodegenerative disease) and to assess the presence or absence of HE. Autopsy reports were reviewed for liver pathology and toxicology.

Results:  Analysis revealed that cases of alcohol abuse had a lower mean (±SD) brain pH, 6.46 (±0.3) as compared with the control mean 6.64 (±0.2). The mean RIN for the alcohol abuse group was 6.97 (±1.3) and controls 7.66 (±0.5). The severity of liver pathology affected both brain pH (< 0.0001) and RIN (< 0.0001). The comparison between cirrhotic cases highlighted increased degradation of RNA in cases with cirrhosis resulting in HE (p = 0.0095). A similar effect was seen on brain pH (p = 0.0019).

Conclusions:  The results show that the presence of cirrhosis and, more so, HE reduces the pH and RIN of postmortem brain tissue.

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