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

  • Mrugesh Thakkar
  • Jurian Edelenbos
  • Sylvain DoréEmail author
Article

Abstract

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.

Keywords

Antioxidant Ischemia Outcomes Protection Treatment 

Abbreviations

AIS

acute ischemic stroke

CHD

coronary heart disease

CRP

C-reactive protein

HDL

high-density lipoprotein

HO1

heme oxygenase 1

HR

hazard ratio

ICAM

intracellular adhesion molecule

IS

ischemic stroke

LAA

large artery atherosclerosis

LACI

laclunar infarction

LDL

low-density lipoprotein

MAPK

mitrogen-activated protein kinase

NADPH

nicotinamide adenine dinucleotide phosphate

NFĸB

nuclear factor kappa B cells

OR

odds ratio

PACI

partial anterior circulation infarction

POCI

posterior circulation infarction

PTEN

phosphatase and tensin homolog

Q

quartile

SAO

small-artery occlusion

SCE

cardioembolic stroke

SD

standard deviation

SUE

stroke of undetermined etiology

SNP

single-nucleotide polymorphisms

TACI

total anterior circulation infarction

TIA

transient ischemic attack

TNF

tumor necrosis factor

UGT

uridine diphosphate glucuronosyltransferase

VCAM

vascular cell adhesion protein

GGT

gamma-glutamyl transpeptidase

UCB

unconjugated bilirubin.

Notes

Acknowledgements

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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