The blood-brain barrier (BBB) is a highly selective interface separating the circulating blood from the brain and spinal cord, collectively known as the central nervous system (CNS). This specialized filtering layer of cells surrounds blood vessels in the brain. Its purpose is to maintain a stable environment within the brain, necessary for proper neural function. The BBB acts as a gatekeeper, preventing harmful substances from entering while allowing necessary nutrients to pass through.
The Unique Architecture
The blood-brain barrier is formed by several cellular and structural components. Brain endothelial cells line the capillaries of the brain, forming the innermost layer. Unlike endothelial cells in other parts of the body, these cells have exceptionally strong “tight junctions” that connect them. These tight junctions act like a zipper, creating a seal that largely prevents substances from slipping between the cells, a pathway known as paracellular movement.
Surrounding these endothelial cells are pericytes, embedded within the capillary basement membrane. Pericytes contribute to the structural integrity and regulation of the BBB’s permeability. The outermost layer includes astrocyte end-feet, which are projections from star-shaped glial cells called astrocytes. These end-feet wrap around the blood vessels, providing structural and metabolic support, and influencing the tightness of the endothelial junctions.
Shielding the Brain from Harm
The blood-brain barrier protects brain tissue from circulating threats. It acts as a selective filter, actively preventing harmful substances from entering the brain. This includes pathogens like viruses and bacteria, as well as toxins present in the bloodstream.
The tight junctions between the endothelial cells are effective in blocking the passage of large molecules. Brain capillaries also lack fenestrations, small pores found in capillaries elsewhere in the body, further contributing to the barrier’s impermeability. The barrier also helps buffer the brain from sudden fluctuations in blood composition, such as changes in ion levels or hormones, which could disrupt the brain’s electrical and chemical activity.
Orchestrating Brain Environment and Supply
Beyond its protective role, the blood-brain barrier actively manages the brain’s internal environment and nutrient supply. It has specific transporter proteins that allow essential nutrients to enter the brain from the bloodstream. This includes molecules like glucose, the brain’s primary energy source, as well as essential amino acids and vitamins.
The BBB also removes metabolic waste products generated by brain activity. It utilizes efflux transporters, which actively pump waste molecules out of the brain. This active management of substance entry and exit maintains the precise chemical balance within the brain, a state known as homeostasis, important for neuronal function.
Impact on Brain Health and Medicine
The integrity and function of the blood-brain barrier have implications for brain health and medical treatments. When the BBB is compromised or “leaky,” it can contribute to various neurological disorders. Conditions such as neuroinflammation, multiple sclerosis, Alzheimer’s disease, stroke, and brain infections can be exacerbated by a dysfunctional barrier, allowing harmful substances or immune cells to enter the brain.
The restrictive nature of the BBB also presents a challenge for delivering therapeutic drugs to the brain. Most medications, especially large-molecule drugs, are unable to cross this barrier effectively. This limitation impacts the treatment of brain tumors and neurodegenerative diseases, as target tissues may not receive sufficient drug concentrations. Researchers are exploring strategies to overcome this obstacle, including approaches to temporarily open or bypass the BBB, or to design drugs that can more readily traverse it.