TRPV4 channel expression and function in blood‐brain barrier (BBB) microvessel endothelial cells

Liver failure is often associated with hepatic encephalopathy, due to dyshomeostasis of the central nervous system (CNS). Under physiological conditions, the CNS homeostasis is precisely regulated by the blood-brain barrier (BBB). The BBB consists of brain microvessel endothelial cells connected with a junctional complex by the adherens junctions and tight junctions. Its main function is to maintain brain homoeostasis via limiting the entry of drugs/toxins to brain. The brain microvessel endothelial cells are characterized by minimal pinocytotic activity, absent fenestrations, and highly expressions of ATP-binding cassette (ABC) family transporters (such as P-glycoprotein, breast cancer resistance protein and multidrug resistance-associated proteins). These ABC transporters prevent brain from toxin accumulation by pumping toxins out of brain. Accumulating evidences demonstrates that liver failure diseases altered the expression and function of ABC transporters at The BBB, indicating that the alterations subsequently affect drugs’ brain distribution and CNS activity/neurotoxicity. ABC transporters also mediate the transport of endogenous substrates across the BBB, inferring that ABC transporters are also implicated in some physiological processes and the development of hepatic encephalopathy. This paper focuses on the alteration in the BBB permeability, the expression and function of ABC transporters at the BBB under liver failure status and their clinical significances.

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Blood-Brain Barrier Dysfunction in the Detrimental Brain Function

10.5772/intechopen.94572 ◽

2021 ◽

Author(s):

Alejandro Gonzalez-Candia ◽

Nicole K. Rogers ◽

Rodrigo L. Castillo

Keyword(s):

Endothelial Cells ◽

Blood Brain Barrier ◽

Brain Function ◽

Neurovascular Unit ◽

Cell Types ◽

Brain Barrier ◽

Barrier Dysfunction ◽

Microvascular Endothelium ◽

Blood Brain ◽

And Function

The blood circulation interface and the neural tissue feature unique characteristics encompassed by the term blood -brain barrier (BBB). The barrier’s primary functions are maintenance of brain homeostasis, selective transport, and protection, all of them determined by its specialized multicellular structure. The BBB primarily exists at the level of the brain microvascular endothelium; however, endothelial cells are not intrinsically capable of forming a barrier. Indeed, the development of barrier characteristics in cerebral endothelial cells requires coordinated cell–cell interactions and signaling from glial cells (i.e., astrocytes, microglia), pericytes, neurons, and extracellular matrix. Such an intricate relationship implies the existence of a neurovascular unit (NVU). The NVU concept emphasizes that the dynamic BBB response to stressors requires coordinated interactions between various central nervous system (CNS) cell types and structures. Every cell type makes an indispensable contribution to the BBBs integrity, and any cell’s failure or dysfunction might result in the barrier breakdown, with dramatic consequences, such as neuroinflammation and neurodegeneration. This chapter will focus on the structure and function of the BBB and discuss how BBB breakdown causes detrimental brain function.

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