Targeting cholestasis induced encephalopathy by inhibition of bile acid reabsorption.

Children with neonatal cholestasis (NC) are at high risk of neurodevelopmental delays and motor impairments. The NC is associated with elevated plasma levels of bile acids (BA) that can accumulate in the brain and induce neuropathology. Using in vitro approaches, we aim to identify BA-specific pathological effects on neurons and glial cells and assess how a sodium-dependent bile acid transporter (ABST) inhibitor affects the function of these cells in vitro. Furthermore, using a surgically induced piglet model of NC, we aim to investigate the BA-specific effects on neurodevelopment in vivo by blocking BA reabsorption in kidneys. Our results may offer a novel strategy to reduce clinical symptoms of cholestasis and serve as a novel approach to alleviate encephalopathies related to NC.