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Spontaneous development of cerebrovascular pathology and microinfarcts in a mouse model of sickle cell disease

View ORCID ProfileHyacinth I. Hyacinth, Cortney L. Sugihara, Thomas L. Spencer, David R. Archer, Andy Y. Shih
doi: https://doi.org/10.1101/103309
Hyacinth I. Hyacinth
1Aflac Cancer and Blood Disorder Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
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  • For correspondence: hhyacinth@emory.edu
Cortney L. Sugihara
2Neuroscience and Behavioral Biology Program, Emory University, Atlanta, GA
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Thomas L. Spencer
3Department of Mechanical Engineering, Georgia Technical Institute, Atlanta, GA
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David R. Archer
1Aflac Cancer and Blood Disorder Center, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA
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Andy Y. Shih
4Department of Neurosciences and
5Center for Biomedical Imaging, Medical University of South Carolina, Charleston, South Carolina
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ABSTRACT

Stroke is a dramatic complication of sickle cell disease (SCD) and is associated with aneurysms, moya moya, intravascular thrombi, cerebral hyperemia and increased vessel tortuosity. We show that aged SCD mice spontaneously develop the characteristics features of cerebral vasculopathy seen in human SCD. Thirteen month old Townes SCD mice and age-matched controls had a cranial windows implanted over the somatosensory cortex. Cortical capillaries were imaged using in vivo two-photon microscopy after the blood plasma was labeled with a fluorescent dye. Results showed that SCD mice compared to controls, had significantly higher red blood cell (RBC) velocity and capillary vessel diameter. SCD mice also had a significantly higher number of occlusive events in the capillary bed, resulting in more stalling of RBC flow. Microvascular topology was also altered, as SCD mice had significantly higher vessel tortuosity and shorter capillary branch lengths. Finally, post-mortem analyses revealed a greater number of cortical microinfarcts, likely caused by vascular occlusion since local tissue hypoxia and blood-brain barrier leakage was prominent. We concluded that aged Townes sickle cell mice spontaneously develop SCD-associated cerebral vasculopathy, and that in vivo two-photon imaging is a powerful approach to investigate the mechanisms of vascular complications in SCD.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 27, 2017.
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Spontaneous development of cerebrovascular pathology and microinfarcts in a mouse model of sickle cell disease
Hyacinth I. Hyacinth, Cortney L. Sugihara, Thomas L. Spencer, David R. Archer, Andy Y. Shih
bioRxiv 103309; doi: https://doi.org/10.1101/103309
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Spontaneous development of cerebrovascular pathology and microinfarcts in a mouse model of sickle cell disease
Hyacinth I. Hyacinth, Cortney L. Sugihara, Thomas L. Spencer, David R. Archer, Andy Y. Shih
bioRxiv 103309; doi: https://doi.org/10.1101/103309

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