The choroid plexus: a door between the blood and the brain for tissue-type plasminogen activator.

In the vascular compartment, the serine protease tissue-type plasminogen activator (tPA) promotes fibrinolysis, justifying its clinical use against vasculo-occlusive diseases. Accumulating evidence shows that circulating tPA (endogenous or exogenous) also controls brain physiopathological processes, like cerebrovascular reactivity, blood-brain barrier (BBB) homeostasis, inflammation and neuronal fate. Whether this occurs by direct actions on parenchymal cells and/or indirectly via barriers between the blood and the central nervous system (CNS) remains unclear. Here, we postulated that vascular tPA can reach the brain parenchyma via the blood-cerebrospinal fluid barrier (BCSFB), that relies on choroid plexus (CP) epithelial cells (CPECs).