Blood-brain barrier

The concept of the blood-brain barrier (BBB) was first articulated by researchers Paul Ehrlich and Edwin Goldmann in the early 20th century. They utilized a vital dye known as trypan blue, a vital stain that can selectively stain living cells or tissues without causing cell death. Trypan blue is particularly valuable in distinguishing dead or damaged cells, as living cells can exclude the dye. Notably, the researchers observed that the dye was not present in the central nervous system (CNS) tissues, suggesting a protective mechanism in place.

The BBB is a critical interface between the bloodstream and the brain, spinal cord, and peripheral nerves. It primarily protects the neural environment, acting as a stabilizing barrier that holds back potential harm while facilitating essential nutrient transport. The specialized type of capillaries that make up the blood-brain barrier are referred to as continuous capillaries. These capillaries are characterized by tight junctions between the endothelial cells, resulting in the absence of fenestrations and a significantly reduced capacity for transcytotic vesicular transport. This structural arrangement is vital for restricting the passage of large molecules and potentially harmful substances, thus maintaining the stable microenvironment necessary for optimal brain function. Astrocytes, a type of glial cell abundant in the CNS, play a crucial role in the functioning of the BBB. They express specific transport mechanisms, such as lipid transporters, which help eliminate lipid-soluble neurotoxins from the brain. One key protein involved in this process is P-glycoprotein (P-gp), or multidrug resistance protein 1. These astrocytes also regulate tight junction integrity and nutrient transport across the barrier. They are instrumental in maintaining ion homeostasis and facilitating neurovascular coupling, which allows for adjusting blood flow in response to neuronal activity and helps in detoxification processes. In pathological conditions such as CNS tumors, cancer cells can form their capillaries devoid of astrocytic support, resulting in the absence of tight junctions. This can provide valuable diagnostic information regarding the nature and progression of the tumor.

Pericytes on the basement membrane of the circumventing endothelial layer contribute significantly to various functions within the BBB. They regulate capillary blood flow, support endothelial cells, and are involved in forming and maintaining the barrier itself. Additionally, pericytes play an important role in the repair and regeneration of vascular tissue, rendering their presence essential for the proper functioning of the microvascular system. When it comes to permeability, the BBB is highly selective. Large molecules, such as plasma proteins, cannot pass through, as all substances or drugs that bind to plasma proteins cannot penetrate the barrier. Furthermore, despite their size or charge, highly charged molecules and toxic substances are also restricted from entering the CNS. Conversely, small lipid-soluble molecules can traverse the blood-brain barrier effectively. Essential substances like water (H2O), oxygen (O2), carbon dioxide (CO2), and glucose (GLUCOSE provides 90% of the brain's energy) can cross the barrier.