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Abstract #3576

Transgenic mouse model recapitulates brain pathophysiology of sickle cell disease

Lisa M Gazdzinski 1 , Lindsay S Cahill 1 , Yu-Qing Zhou 1 , Albert KY Tsui 2,3 , Gregory MT Hare 2,3 , Andrea Kassner 4,5 , and John G Sled 1,6

1 Mouse Imaging Centre, Hospital for Sick Children, Toronto, Ontario, Canada, 2 Department of Anaesthesia, St. Michael's Hospital, Toronto, Ontario, Canada, 3 Keenan Research Centre for Biomedical Science, University of Toronto, Ontario, Canada, 4 Department of Medical Imaging, University of Toronto, Ontario, Canada, 5 Department of Physiology and Experimental Medicine, Hospital for Sick Children, Toronto, Ontario, Canada, 6 Department of Medical Biophysics, University of Toronto, Ontario, Canada

Sickle cell disease (SCD) is associated with neurocognitive impairment and an increased risk of stroke. The mechanisms are poorly understood, but likely involve increased cerebral blood flow (CBF) and decreased cerebrovascular reserve (CVR). This study uses CASL to characterize CBF and CVR in a transgenic mouse model of SCD, demontrating that the model recapitulates important pathophysiological features of the disease. Brain morphometry is also performed using high-resolution MRI, showing localized volume differences throughout the brain in SCD mice. The model characterized here will be invaluable for developing an understanding of the mechanisms behind stroke and neurocognitive impairment in SCD.

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