Researchers discovered that cerebrovascular responsiveness to carbon dioxide in patients with sickle cell disease (SCD) is reduced compared with healthy individuals, according to a study published in Physiological Reports. 

Patients with SCD have a high risk of developing cerebral infarction and hemorrhage due to the presence of sickle-shaped erythrocytes, which have a reduced affinity for oxygen. However, the precise pathophysiology of SCD neurological complications has yet to be fully explored in the medical literature. 

When the brain lacks sufficient oxygen, compensatory mechanisms turn on to maintain oxygenation to cerebral tissue. This is believed to be accomplished by increasing the diameter of cerebral vessels. However, studies indicate that these compensatory mechanisms are likely to be incomplete, resulting in multiple tissue infarctions. 

The authors of the study hence set out to investigate the ability of cerebral vessels to dilate in response to reduced cerebral oxygenation. They recruited 35 patients with SCD, as well as 24 healthy control volunteers. Participants who had white matter hyperintensities on a brain scan and strokes were excluded from the study. 

Read more about SCD etiology 

The research team used magnetic resonance imaging to investigate the ability of patients with SCD to respond to a vasoactive stimulus. The areas under investigation were the anterior, middle, and posterior cerebral artery territories. 

“Cerebrovascular reactivity was measured as the blood oxygen level dependent signal (a surrogate for cerebral blood flow) response to an increase in the end tidal partial pressure of CO2,” the authors wrote. “The dynamic aspect of the response was measured as the time constant of the first order response kinetics (tau).”

The results of the study indicate that patients with SCD had poorer cerebrovascular reactivity compared with the control group; with regard to the speed of the response to CO2, the researchers discovered that the tau and transfer function analysis were higher in the group of patients with SCD compared with the control.

“The main findings are that in patients with SCD, [cerebrovascular reactivity], gain and coherence are reduced in the [regions of interest] while tau and phase are increased, indicating a decreased and slower response,” the authors concluded. 


Sayin ES, Sobczyk O, Poublanc J, et al. Assessment of cerebrovascular function in patients with sickle cell disease using transfer function analysisPhysiol Rep. 2022;10(19):e15472. doi:10.14814/phy2.15472