The blood–brain barrier: a help and a hindrance

The blood-brain barrier (BBB) is a specialized vascular structure that protects the brain micro-environment from toxins and pathogens in the blood. At the same time, the BBB presents a significant challenge for drug development, as it restricts the entry of most therapeutics into the brain. In this review, we first examine recent findings on the molecular and cellular architecture of the BBB, emphasizing the diverse mechanisms that facilitate the transport and exchange of molecules between the blood and the brain. We discuss current knowledge on the heterogeneity of the BBB along the arteriovenous axis and across different brain regions. Then, we explore the molecular and functional changes in the BBB that occur during normal ageing, neurodegeneration and acute brain injuries, and how prolonged BBB impairment affects transport mechanisms and disease progression. Additionally, we discuss novel developments in drug delivery strategies to transport small molecules, biologicals or cellular therapeutics across the BBB. Finally, we examine therapeutic opportunities to restore the BBB and discuss future directions in the field.