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

O’Connell, Grant C.; Treadway, Madison B.; Petrone, Ashley B.; Tennant, Connie S.; Lucke-Wold, Noelle; Chantler, Paul D.; Barr, Taura L.

The results of our in vitro experiments supported this hypothesis, as the expression levels of the PKA-binding isoforms of AKAP7, along with the expression levels of ITGA3, were elevated on primary lymphocytes which exhibited a strongly adherent phenotype indicative of invasiveness. The presence of a lymphocyte population with such properties in the peripheral immune system following stroke could contribute to disruption of the BBB by both direct and indirect mechanisms. The process of cerebrovascular lymphocyte extravasation alone inherently reduces the integrity of the BBB 32 , and heightened accumulation of lymphocytes in the brain parenchyma increases the risk of further BBB disruption via the development an adaptive immune response directed at central nervous system antigens 33 . The development of such a response leads to lymphocyte-mediated production of pro-inflammatory chemokines which drive increased influx of innate immune cell populations such as neutrophils and monocytes from the periphery into the central nervious system 34 ; during this process, these myeloid immune populations produce proteolytic molecules such as matrix metalloproteinases which further act to compromise the integrity of the BBB 2 . Expectedly, it has been shown in multiple studies that increased lymphocyte activity post-stoke leads to poor prognosis 35, 36 . Thus, our results suggest that AKAP7 and ITGA3 are molecules which could potentially be targeted therapeutically to limit lymphocyte-mediated post-stroke injury exacerbation.