Abstract Objectives Stroke in sickle cell disease (SCD) is often attributed to large vessel involvement in the disorder, whereas the contribution of cerebral microvascular disease has been less explored. In this study, we investigated the formation of cerebral microvascular lesions and the involvement of mast cells in a humanized SCD mouse model. Methods We studied hemorrhagic microvascular disease in a well-characterized mouse model of humanized transgenic sickle (HbSS-BERK) expressing 99% human sickle hemoglobin (HbS) and a control (HbAA-BERK) mouse model expressing normal human hemoglobin A (HbA). Mouse brains were analyzed by Prussian blue staining to detect cerebral microhemorrhage (CMH) formation. Mast cell identification was performed by Toluidine Blue staining. Results SCD brain sections exhibited approximately 86% more CMH than controls (mean ± SE of 1.17 ± 0.22 vs 0.63 ± 0.13 number/cm2, p = 0.02). Mast cells positively correlated with CMH number in SCD mice (Spearman r = 0.42, p 0.05), but not in control mice. Conclusion In conclusion, SCD mice demonstrated significantly increased CMH load compared with control mice, and SCD microhemorrhages were associated with the number of mast cells. These findings highlight the significance of cerebral microvascular disease in SCD and imply that cerebral mast cells may be a novel therapeutic target in SCD.
Hung et al. (2026) studied this question.