Bilirubin and Ischemic Stroke: Rendering the Current Paradigm to Better Understand the Protective Effects of Bilirubin

  • Mrugesh Thakkar
  • Jurian Edelenbos
  • Sylvain Doré


Novel and innovative methods are critical in fostering new treatments and improving clinical outcomes in patients who suffer from ischemic stroke. Bilirubin has long been considered metabolic waste that can be harmful to the body; however, it is now becoming recognized as one of the body’s most potent antioxidant, anti-inflammatory, and neuroprotective molecules. These properties facilitate bilirubin’s anti-atherogenic effects to impede and prevent the formation of thrombi in ischemic stroke. These functions allow for protection from neuronal injury during an ischemic state and suggest that elevated bilirubin levels may be linked to a lower rate of morbidity and mortality. Therefore, here we discuss the pathophysiology of stroke and the molecular properties of bilirubin to better understand their beneficial relationship. We outline clinical studies looking at the relationship between serum bilirubin levels and ischemic stroke prevalence. At this time, few studies have rigorously looked at the relationship between bilirubin and ischemic stroke, whether it is positive or negative. Thus, rigorous research is needed to provide evidence supporting the current studies, expand on these studies, and facilitate their translation to bedside therapy for patients who suffer from ischemic stroke.


Antioxidant Ischemia Outcomes Protection Treatment 



acute ischemic stroke


coronary heart disease


C-reactive protein


high-density lipoprotein


heme oxygenase 1


hazard ratio


intracellular adhesion molecule


ischemic stroke


large artery atherosclerosis


laclunar infarction


low-density lipoprotein


mitrogen-activated protein kinase


nicotinamide adenine dinucleotide phosphate


nuclear factor kappa B cells


odds ratio


partial anterior circulation infarction


posterior circulation infarction


phosphatase and tensin homolog




small-artery occlusion


cardioembolic stroke


standard deviation


stroke of undetermined etiology


single-nucleotide polymorphisms


total anterior circulation infarction


transient ischemic attack


tumor necrosis factor


uridine diphosphate glucuronosyltransferase


vascular cell adhesion protein


gamma-glutamyl transpeptidase


unconjugated bilirubin.



The authors wish to thank members of the Doré Lab and the University of Florida Center for Translational Research in Neurodegenerative Disease.

Funding Information

Part of the funding to support this work was provided by grants from the NIH, the AHA, Brain Aneurysm Foundation, and the Department of Anesthesiology.


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Authors and Affiliations

  1. 1.Department of Anesthesiology, Center for Translational Research in Neurodegenerative DiseaseMcKnight Brain Institute, University of FloridaGainesvilleUSA
  2. 2.Departments of Neurology, Psychiatry, Pharmaceutics, Psychology, and NeuroscienceUniversity of Florida College of MedicineGainesvilleUSA

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