Animal Kernicterus Models: Progress and Challenges

Kernicterus is a leading cause of neonatal death throughout the world, especially in low-middle-income countries. It is developed by an unconjugated hyperbilirubinemia in the blood and brain tissue, triggering pathological processes that spawn neurotoxicity and neurodegeneration. However, the biological mechanism (s) of bilirubin-induced neurotoxicity and Kernicterus development remain to be well elucidated. Likewise, a practical therapeutic approach for human Kernicterus has yet to be found. Undoubtedly, animal models of Kernicterus can be helpful in the identification of underlying biological processes of hyperbilirubinemia evolution to Kernicterus, as well as the evaluation of various treatments efficacy in preclinical studies. More importantly, establishing an animal model that can mimic the Kernicterus and its behavioral, neuro-histological, and hematological manifestations is a severe priority in preclinical studies. So far, several Kernicterus animal models have been established that could partially mimic one or more clinical and paraclinical signs of human Kernicterus. The present study aimed to review all methods modeling Kernicterus with a focus on their potentials and shortcomings and subsequently provide the optimal methods for an ideal Kernicterus animal model.