Pathophysiology of cerebral glutamate transport dysfunction in acute liver failure

• Grant number: 11/02263-3
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2012
• End date: February 28, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Alan Stewart Hazell
• Grantee: Alan Stewart Hazell
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Acute liver failure (ALF) arising from viral infection or toxic liver injury is a serious metabolic disorder with life-threatening consequences. Hepatic encephalopathy and the associated cerebral edema arising from ALF demands immediate attention usually necessitating emergency liver transplantation. Understanding the pathophysiology of this disorder is necessary in order to develop rational therapeutic strategies. We will perform this investigation using 1) an established drug-induced mouse model of ALF which recapitulates many of the pathophysiological changes observed in the human disorder, and 2) primary cultures of astrocytes. These studies will evaluate the involvement of glutamatergic dysfunction in different ways and potential therapeutic strategies using in vivo microdialysis, immunoblotting, immunohistochemistry, quantitative autoradiography, antisense and RNA interference knockdown strategies, cerebral edema measurements, and the calcium channel blocker nicardipine. The findings are expected to yield new insight into the pathophysiology of ALF and could lead to new future treatments for this life-threatening condition. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE MOURA, THATIANE C.; AFADLAL, SZEIFOUL; HAZELL, ALAN S.. Potential for stem cell treatment in manganism. NEUROCHEMISTRY INTERNATIONAL, v. 112, p. 134-145, JAN 2018. (11/02263-3, 11/02295-2, 13/07559-3)

VEMUGANTI, RAGHU; SILVA, VINICIUS R.; MEHTA, SURESH L.; HAZELL, ALAN S.. Acute liver failure-induced hepatic encephalopathy is associated with changes in microRNA expression profiles in cerebral cortex of the rat. METABOLIC BRAIN DISEASE, v. 29, n. 4, p. 9-pg., 2014-12-01. (12/15660-3, 11/02263-3)

VEMUGANTI, RAGHU; SILVA, VINICIUS R.; MEHTA, SURESH L.; HAZELL, ALAN S.. Acute liver failure-induced hepatic encephalopathy is associated with changes in microRNA expression profiles in cerebral cortex of the rat. METABOLIC BRAIN DISEASE, v. 29, n. 4, SI, p. 891-899, DEC 2014. (12/15660-3, 11/02263-3)