Clinical Implications of Bilirubin-Associated Neuroprotection and Neurotoxicity

Bilirubin is a primary product of heme catabolism and exhibits both neuroprotective and neurotoxic effects. When present at physiologic concentrations, bilirubin is a potent antioxidant and serves to protect brain tissue from oxidative stress insults. The use of the anesthetic propofol attenuates ischemic injury in rats by exploiting these neuroprotective properties. At pathologic levels, bilirubin has been implicated as a neurotoxic agent, demonstrating the ability to aggregate and adhere to cellular membranes, thereby disrupting normal cellular function. Bilirubin-associated toxicities are amplified by administering drugs such as anesthetics that compete with bilirubin for albumin binding sites, resulting in increased plasma bilirubin concentrations. As such, it is crucial that bilirubin is considered in the critical care management of patients with hemorrhagic stroke, cerebral ischemic damage, and critically ill newborns.