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Decreased cerebral perfusion correlates with increased BOLD hyperoxia response in transgenic mouse models of sickle
Richard P Kennan1, Sandra M Suzuka, Ronald L Nagel
1Department of Medicine, Division of Hematology, Albert Einstein College of Medicine, Bronx, New York 10461, USA. rkennan@aecom.yu.edu
Abstract:
Neurological complications such as stroke are known consequences of sickle cell disease (SCD). In order to improve methods for the evaluation of stroke risk in SCD, MRI was used to evaluate cerebrovascular function in transgenic mouse models of human SCD. It is hypothesized that oxygen-sensitive imaging in the brain will reveal areas of excess deoxygenation that are either at risk of or the result of vaso-occlusion. Arterial spin labeling (ASL) perfusion was performed in order to correlate BOLD results with microvascular cerebral blood flow. Upon comparison with control animals, there was a relative increase in BOLD hyperoxia response of 42-67% (P < 0.001) in the transgenic mice while cerebral blood flow during normoxia was reduced by 30-40% (P < 0.02). Hyperoxia caused cerebral blood flow to decrease in control mice, whereas blood flow increased in the sickle transgenic mice. These results indicate impairment in brain autoregulation in the sickle cell transgenic mice leading to increased cerebral deoxyhemoglobin. Increased deoxyhemoglobin coupled with reduced perfusion may further increase the risk of vaso-occlusion and stroke. This may reflect polymer reduction or reduced cell adhesion during hyperoxia. The MRI protocol is noninvasive and thus directly applicable to a clinical population.
Insights
Sickle cell disease (SCD) mice show impaired brain blood flow regulation and increased deoxyhemoglobin, indicating higher stroke risk. Noninvasive MRI reveals these changes, aiding clinical stroke risk evaluation in SCD patients.
Area of Science:
- Neurology
- Medical Imaging
- Hematology
Background:
- Sickle cell disease (SCD) is associated with significant neurological complications, including stroke.
- Current methods for evaluating stroke risk in SCD require improvement for better patient outcomes.
Purpose of the Study:
- To investigate cerebrovascular function in transgenic mouse models of human SCD using MRI.
- To identify potential biomarkers for stroke risk assessment in SCD.
Main Methods:
- Utilized oxygen-sensitive MRI techniques, including Blood Oxygen Level-Dependent (BOLD) imaging and Arterial Spin Labeling (ASL) perfusion.
- Compared cerebrovascular responses to hyperoxia between SCD transgenic mice and control animals.
Main Results:
- SCD mice exhibited a 42-67% greater BOLD hyperoxia response compared to controls (P < 0.001).
- Cerebral blood flow was reduced by 30-40% in SCD mice during normoxia (P < 0.02).
- Hyperoxia decreased cerebral blood flow in controls but increased it in SCD mice, suggesting impaired autoregulation.
Conclusions:
- Transgenic SCD mice demonstrate impaired brain autoregulation, leading to increased cerebral deoxyhemoglobin and reduced perfusion.
- These MRI findings suggest a heightened risk of vaso-occlusion and stroke in SCD.
- The noninvasive MRI protocol is suitable for clinical application in evaluating stroke risk in SCD patients.
