Peripheral blood AKAP7 expression as an early marker for lymphocyte-mediated post-stroke blood brain barrier disruption

Abstract

Abstract Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging. Early heightened expression levels of AKAP7, a gene encoding a protein kinase A-binding scaffolding molecule, were significantly associated with BBB disruption 24 hours post-hospital admission. We then determined that AKAP7 is predominantly expressed by lymphocytes in peripheral blood, and strongly co-expressed with ITGA3, a gene encoding the adhesion molecule integrin alpha 3. Subsequent in vitro experiments revealed that heightened expression of AKAP7 and ITGA3 in primary human lymphocytes is associated with a highly adherent phenotype. Collectively, our results suggest that AKAP7 expression levels may have clinical utility as a prognostic biomarker for post-stroke BBB complications, and are likely elevated early in patients who later develop post-stroke BBB disruption due to the presence of an invasive lymphocyte population in the peripheral blood.