Increased expression of P2X7 receptor during the blood-brain barrier opening by low-intensity focused ultrasound

Abstract

The combination of focused ultrasound (FUS) and the microbubbles allows non-invasive and localized opening of the blood-brain barrier (BBB), which is transient and potentially safe. This study aimed to understand the mechanism underlying the focused ultrasound mediated opening of the BBB. In this regard, I hypothesized that the BBB opening process induced by FUS may involve IL-1β signaling through the P2X7 receptor. The extravasation of Evans Blue was performed and analyzed to quantify the BBB opening by FUS. Since some of the detailed changes that take place in the tight junction proteins of the cerebral microvascular endothelium could result because of the sonication combined with microbubbles, I evaluated the time-dependent expression levels of the tight junction proteins. Also, I examined the expression level of P2X7 receptor after FUS in time-dependent manner. Any cellular damage that could occur in a series of BBB opening by FUS was examined by expression levels of NF-κB and determination of early apoptotic population by TUNEL assay. This study makes a contribution to the literature because it shows that increased expression of P2X7 and activation of P2X7 signaling pathway by FUS may be related to the BBB opening mechanism. Also, I can provide insights into the mechanism involved in the modulation of BBB opening.