| Grant number: | 11/02263-3 |
| Support type: | Regular Research Grants |
| Duration: | March 01, 2012 - February 28, 2015 |
| Field of knowledge: | Health Sciences - Medicine |
| Principal researcher: | Alan Stewart Hazell |
| Grantee: | Alan Stewart Hazell |
| Home 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)