期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 39, 期 2, 页码 342-351出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X17732275
关键词
Sickle cell disease; stroke; cerebral vasculopathy; cerebral blood flow; hematology
资金
- Emory University Pediatrics Pilot Grant (HeRO)
- NIH/NHLBI [U01HL117721, R01HL138423]
- NINDS [R21NS085402, R01NS097775]
- Dana Foundation
- South Carolina Clinical and Translational Institute [UL1TR000062]
- Institutional Development Award (IDeA) from the NIGMS [P20GM12345]
- Charleston Conference on Alzheimer's Disease New Vision Award
Stroke is a dramatic complication of sickle cell disease (SCD), which is associated with cerebral vasculopathies including moya moya, intravascular thrombi, cerebral hyperemia, and increased vessel tortuosity. The spontaneous occurrence of these pathologies in the sickle cell mouse model has not been described. Here, we studied Townes humanized sickle cell and age-matched control mice that were 13 months old. We used in vivo two-photon microscopy to assess blood flow dynamics, vascular topology, and evidence of cerebral vasculopathy. Results showed that compared to controls, sickle cell mice had significantly higher red blood cell (RBC) velocity (0.73 mm/s vs. 0.55 mm/s, p = 0.013), capillary vessel diameter (4.84 mu M vs. 4.50 mu M, p = 0.014), and RBC volume flux (0.015 nL/s vs. 0.010 nL/s, p = 0.021). Also, sickle cell mice had significantly more tortuous capillary vessels (p < 0.0001) and significantly shorter capillary vessel branches (p = 0.0065) compared to controls. Sickle cell mice also had significantly higher number of capillary occlusive events (3.4% vs. 1.9%, p < 0.0001) and RBC stalls (3.8% vs. 2.1%, p < 0.0001) in the cerebral capillary bed. In post-mortem immunohistochemical analyses, sickle cell mice had a 2.5-fold higher frequency of cortical microinfarcts compared to control mice. Our results suggest that aged Townes sickle cell mice spontaneously develop SCD-associated cerebral vasculopathy.
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