The Blood–Brain Barrier

The Blood–Brain Barrier

2015 | Richard Daneman and Alexandre Prat
The blood-brain barrier (BBB) is a specialized structure in the central nervous system (CNS) that tightly regulates the exchange of substances between the blood and the brain. It is formed by endothelial cells (ECs) in the microvasculature, which are supported by mural cells, astrocytes, and immune cells. The BBB ensures proper neuronal function by maintaining CNS homeostasis, protecting against toxins and pathogens, and preventing the entry of harmful substances. However, dysfunction of the BBB is a key factor in many neurological diseases, including multiple sclerosis (MS), stroke, Alzheimer's disease, and traumatic brain injury. The BBB is characterized by tight junctions (TJs) that limit paracellular transport, low transcytosis, and the expression of efflux transporters that prevent the entry of lipophilic molecules. CNS ECs also have a unique metabolic profile, with high levels of mitochondria and low levels of leukocyte adhesion molecules (LAMs), which restrict immune cell entry. The BBB is regulated by interactions between ECs, mural cells, astrocytes, and immune cells, forming the neurovascular unit. Pericytes, which are embedded in the basement membrane, play a critical role in regulating BBB formation and function, as well as in maintaining vascular homeostasis. Astrocytes contribute to BBB function by providing a cellular link between the CNS and blood vessels, and by secreting factors that modulate BBB properties. They also regulate blood flow in response to neuronal activity. Immune cells, such as perivascular macrophages and microglia, interact with the BBB and can influence its function during inflammation or disease. The BBB is also regulated by various signaling pathways, including Wnt/β-catenin, Hedgehog, and TGF-β, which are involved in BBB formation, maintenance, and response to injury. The BBB is composed of multiple components, including TJs, transporters, and metabolic enzymes, which work together to maintain the barrier. Dysfunction of the BBB can lead to increased permeability, allowing the entry of immune cells and harmful substances into the CNS, which can cause neuronal damage and disease progression. Understanding the molecular and cellular mechanisms that regulate the BBB is essential for developing therapies to treat neurological disorders. Current research focuses on identifying new targets for drug delivery across the BBB and understanding how the BBB responds to injury, inflammation, and disease.The blood-brain barrier (BBB) is a specialized structure in the central nervous system (CNS) that tightly regulates the exchange of substances between the blood and the brain. It is formed by endothelial cells (ECs) in the microvasculature, which are supported by mural cells, astrocytes, and immune cells. The BBB ensures proper neuronal function by maintaining CNS homeostasis, protecting against toxins and pathogens, and preventing the entry of harmful substances. However, dysfunction of the BBB is a key factor in many neurological diseases, including multiple sclerosis (MS), stroke, Alzheimer's disease, and traumatic brain injury. The BBB is characterized by tight junctions (TJs) that limit paracellular transport, low transcytosis, and the expression of efflux transporters that prevent the entry of lipophilic molecules. CNS ECs also have a unique metabolic profile, with high levels of mitochondria and low levels of leukocyte adhesion molecules (LAMs), which restrict immune cell entry. The BBB is regulated by interactions between ECs, mural cells, astrocytes, and immune cells, forming the neurovascular unit. Pericytes, which are embedded in the basement membrane, play a critical role in regulating BBB formation and function, as well as in maintaining vascular homeostasis. Astrocytes contribute to BBB function by providing a cellular link between the CNS and blood vessels, and by secreting factors that modulate BBB properties. They also regulate blood flow in response to neuronal activity. Immune cells, such as perivascular macrophages and microglia, interact with the BBB and can influence its function during inflammation or disease. The BBB is also regulated by various signaling pathways, including Wnt/β-catenin, Hedgehog, and TGF-β, which are involved in BBB formation, maintenance, and response to injury. The BBB is composed of multiple components, including TJs, transporters, and metabolic enzymes, which work together to maintain the barrier. Dysfunction of the BBB can lead to increased permeability, allowing the entry of immune cells and harmful substances into the CNS, which can cause neuronal damage and disease progression. Understanding the molecular and cellular mechanisms that regulate the BBB is essential for developing therapies to treat neurological disorders. Current research focuses on identifying new targets for drug delivery across the BBB and understanding how the BBB responds to injury, inflammation, and disease.
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