Sickle cell mice exhibit elevated plasma bilirubin and altered intracranial cerebral blood velocities that are exacerbated by hypoxia-reoxygenation.

This article focuses on the effects of hypoxia-reoxygenation on cerebral blood flow velocities and plasma bilirubin levels in a transgenic sickle cell disease (SCD) mouse model. Using transcranial ultrasound, the study found that sickle cell (SS) mice subjected to hypoxic stress exhibited significantly lower relative mean blood flow velocities in the middle cerebral artery (MCA) compared to wild-type (AA) mice, alongside a decreased Lindegaard ratio indicative of vasodilation rather than vasospasm. Additionally, SS mice showed elevated plasma bilirubin levels—a hemolysis marker—which correlated inversely with MCA velocity and the Lindegaard ratio, suggesting bilirubin's potential role in modulating cerebral vascular reactivity under hypoxic conditions. Despite these vascular changes, no significant cerebral infarction was detected after transient hypoxia-reoxygenation, indicating that hypoxia alone may not induce ischemic injury in this model. The findings highlight a possible interaction between elevated bilirubin and hypoxia in promoting vasodilation in cerebral vessels of SCD mice, warranting further mechanistic investigation.