Blood–brain barrier endothelium (BBB)

The blood–brain barrier (BBB) endothelium is a highly specialized layer of endothelial cells that forms a restrictive semipermeable interface between the systemic blood circulation and the central nervous system (CNS). Its primary biological function is to maintain the brain's microenvironment by strictly regulating the transport of ions, nutrients, and metabolic waste while preventing the entry of neurotoxins and pathogens (Daneman & Prat, 2015). This barrier is maintained by complex tight junctions and a high expression of efflux transporters, such as P-glycoprotein, which actively pump out various pharmacological agents (Abbott et al., 2010). In many pathological states, including stroke and neurodegenerative diseases, the BBB becomes compromised, leading to increased permeability and neuroinflammation (Sweeney et al., 2019). From a drug development perspective, the BBB is a critical hurdle, as it prevents the vast majority of small-molecule and biologic drugs from reaching therapeutic concentrations in the brain (Pardridge, 2012). Consequently, the BBB is targeted both to enhance drug delivery—using strategies like osmotic disruption or receptor-mediated transport—and to restore barrier integrity in diseases where it is pathologically leaky.

Other names

Blood-brain barrierBrain microvascular endothelial cellsNeurovascular unitCerebral endotheliaCell membranes of the blood-brain barrier

Drugs interact with the blood–brain barrier through passive lipid-mediated diffusion, carrier-mediated transport (CMT), receptor-mediated transcytosis (RMT), or by modulating tight junction integrity to increase paracellular permeability (Pardridge, 2012; Abbott et al., 2010).