Patients with sickle cell anemia (SCA) have abnormal hemoglobin (sickle hemoglobin S) leading to the crystallization of hemoglobin chains in red blood cells (RBCs), which assume sickle shape and display reduced flexibility. Sickle RBCs (sRBCs) adhere to vessel walls and block blood flow, thus preventing oxygen delivery to the tissues leading to vaso-occlusive crises (VOC), acute pain and organ damage. SCA patients often have chronic pain that can be attributed to inflammation, vasculopathy, neuropathy, ischemia-reperfusion injury and organ damage. Blood oxygenation level-dependent (BOLD) based functional magnetic resonance imaging (fMRI) technique that is commonly used for noninvasively mapping spontaneous or evoked brain activation in human or animal models has been applied in this study to assess abnormal oxygenation change in the brains of mice with SCA in response to hypoxia. We found that hyperalgesic HbSS-BERK sickle mice with chronic pain display reduced BOLD response to a hypoxia challenge compared to their control HbAA-BERK mice. Hypoxia/reoxygenation (H/R) treated sickle mice under acute pain episode exhibit even smaller BOLD signal changes than sickle mice without H/R, suggestive of correlations between cerebral BOLD signal changes and nociception.
Bibliographical noteFunding Information:
This study was supported partly by NIH U01 HL117664 grant to KG, R01 NS070839 to XHZ and R01 MH111413 to WC; Institute for Engineering in Medicine group grant at the University of Minnesota to KG, WC and XHZ; P41 EB015894, P30 NS5076408 and the W.M. Keck Foundation for CMRR facility and resource. We thank Yi Zhang for helping with animal care and fMRI experiment assistance and Ritu Jha and Susan Thompson for breeding sickle and control mice.
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