Description: Chronic hepatic encephalopathy (chronic HE) is a neurological disease caused by chronic liver disease (CLD). Unlike adults, children grow up with significant neurological deficits even after liver transplantation, suggesting that the immature brain is uniquely vulnerable to the insults associated with CLD.
Despite considerable advances in understanding the pathogenesis of many neurological diseases, key questions remain unanswered for chronic HE. What makes the developing brain more vulnerable? What regional brain metabolic changes occur in response to elevated ammonium and its metabolic product glutamine (Gln)? How do these affect the morphology and function of brain cells?
Current therapies aimed at lowering peripheral ammonium load are insufficient to avoid long-term clinical consequences in children. Therefore, identifying novel molecular pathways involved in chronic HE that might be amenable to therapeutic intervention would be a major advance.
The current project aims to address the molecular, regional, and age-dependence changes in chronic HE in vivo and longitudinally using a multi-modal approach based on dynamic multinuclear MRS(I) and MRI at ultra-high filed, PET and ex-vivo histological measures in the adult and developing brain under chronic HE.
Investigator: Cristina Cudalbu (EPFL), Olivier Braissant (CHUV, UNIL), Valerie McLin (HUG, UNIGE)
Collaborators: Katarzyna Pierzchala (EPFL), Dre. Anne-Laure Rougemont (HUG, UNIGE), Dario Sessa (HUG, UNIGE)
PhD students : Dunja Simicic, Jessie Mosso (EPFL)