Document Type
Article
Publication Date
5-15-2025
Abstract
Sickle cell disease (SCD) is a genetic disorder characterized by sickle red blood cells (RBCs). Sickle RBCs cause cerebral vasculopathies including vaso-occlusive events, leading to ischemia-reperfusion injury and hypoxic tissue environment. To date, the physiological blood flow velocities in cerebral vessels of preclinical SCD models has not been evaluated under hypoxic-reoxygenation. In our study, we used transcranial ultrasound techniques to measure abnormal blood flow velocities in the internal carotid (ICA) and middle cerebral arteries (MCA) of transgenic sickle cell mice (SS) challenged with hypoxia-reoxygenation. Our study showed that SS mice that underwent hypoxic stress exhibited lower relative mean velocities in the MCA compared to wildtype mice (AA) (0.67 ± 0.18 vs. 0.95 ± 0.15; p < 0.05). Comparison of the Lindegaard ratio between normoxia and hypoxia in SS mice suggested that the MCA underwent vasodilation (0.67 ± 0.18 vs. 0.95 ± 0.15; p < 0.05). Bilirubin, a potential biomarker for cerebral vasculopathies in SCD, was higher in SS than AA mice (0.56 ± 0.28 vs. 0.05 ± 0.07 mg/dL; p < 0.05). Correlation analyses revealed a significant association between bilirubin levels and blood velocities of MCA (r = −0.9377, p = 0.0002) and ICA (r = 0.8203, p = 0.0068), especially in hypoxic conditions of SS mice. We propose that the reactivity of cerebral vessels in SS mice is correlated with the elevated plasma bilirubin level.
Recommended Citation
Nunez FJ, Mohieldin AM, Pan AY, et al. Sickle cell mice exhibit elevated plasma bilirubin and altered intracranial cerebral blood velocities that are exacerbated by hypoxia-reoxygenation. Journal of Cerebral Blood Flow & Metabolism. 2025;0(0). https://doi.org/10.1177/0271678X251338961
Supplementary Material
Copyright
The authors
Included in
Animal Experimentation and Research Commons, Cardiovascular Diseases Commons, Medical Neurobiology Commons, Other Pharmacy and Pharmaceutical Sciences Commons
Comments
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Cerebral Blood Flow & Metabolism in 2025 following peer review. This article may not exactly replicate the final published version. The definitive publisher-authenticated version is available online at https://doi.org/10.1177/0271678X251338961.