Decreased cerebral perfusion correlates with increased BOLD hyperoxia response in transgenic mouse models of sickle cell disease

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.