Data show the average maximum cortical capillary RBC velocity is significantly greater in sickle cell mice compared to controls.
Noor Mary Abi Rached
A recent study explored the role of aberrant WBC- and/or RBC-endothelial interaction, mediated via vascular cell adhesion molecule-1 (VCAM-1), in the pathophysiology of cerebral microvascular hemodynamics and vasculopathy leading to cerebral microinfarcts in sickle cell disease (SCD).
Led by Noor Mary Abi Rached, Neuroscience and Behavioral Biology, Emory University, a team of investigators hypothesized that sickle cell mice would show greater cerebral cortical expression of VCAM-1 compared with age-matched controls.
Ultimately, they found the high velocity of blood flow might be a mechanical force contributing to cerebral microvascular VCAM-1 expression in sickle cell mice, which may be responsible for increased leukocyte-endothelial interaction and adhesion.
The study was presented at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition.
Abi Rachad and colleagues set out to examine the relationship between abnormalities in cerebral microvascular hemodynamics and VCAM-1 deposition in the cerebral microvasculature. In doing so, they utilized a humanized sickle cell (with HbSS) and the corresponding control (with HbAA).
Following cranial-window procedures, cortical capillaries, precapillary arterioles, and post-capillary venules were then imaged using two-photon microscopy at 2 points of time. They noted the study included pre- and post-transfusion groups.
An analysis of line scans were used to identify the number and duration of rolling or adherent WBCs and RBCs, the RBC velocity in cerebral microvasculature, and frequency and magnitude (mL/sec) of cerebral microvascular blood flow reversals.
They defined rolling WBCs as lasting ≥2 seconds and adherent RBCs were defined as lasting ≥0.5 seconds.
The team used immunohistochemistry to stain 50-micron sections of brain tissue for VCAM-1, Lectin to localize the vasculature, and Neun to localize neuronal nuclei in order to quantify the expression of VCAM-1. Images were analyzed using Phenochart and ImageJ software.
Data show the average maximum cortical capillary RBC velocity is significantly greater in sickle cell mice (HbSS, n = 13) in comparison to controls (HbAA, n = 8), scanned at T1 (P <.001).
Further, they found a significantly higher expression of microvascular VCAM-1 in SS mice, compared to control (P <.001), as well as a significantly higher number of leukocyte rolling (P <.001) in the sickle cell mice, compared to controls.
A significantly higher frequency of blood flow reversals (P <.01) and higher magnitude of microvascular blood flow reversals (P <.001) were observed in sickle cell mice, compared to controls.
An interesting point to note relayed that sickle cell mice have slightly lower average capillary blood flow velocity, but this was not considered statistically significant (P = .079). Investigators expressed their surprise regarding this, due to the differences in frequency and magnitude of microvascular blood flow reversal in sickle cell mice, when compared to controls.
Overall, Abi-Rached and colleagues noted that the high velocity of blood flow might be a mechanical force contributing to cerebral microvascular VCAM-1 expression in sickle cell mice.
“This might be responsible for the increased leukocyte-endothelial interactions and adhesion, ultimately leading to higher frequency and magnitude of cerebral microvascular blood flow reversal,” they wrote.
“Contribution of Vascular Cell Adhesion Molecule to Hemodynamics in Sickle Cell Disease,” was published online by ASH.