The crossroads of neuroinflammation in infectious diseases: endothelial cells and astrocytes (original) (raw)

Disruption of the Blood-Brain Barrier During Neuroinflammatory and Neuroinfectious Diseases

Contemporary Clinical Neuroscience

As the organ of highest metabolic demand, utilizing over 25% of total body glucose utilization via an enormous vasculature with one capillary every 73 μm, the brain evolves a barrier at the capillary and postcapillary venules to prevent toxicity during serum fluctuations in metabolites and hormones, to limit brain swelling during inflammation, and to prevent pathogen invasion. Understanding of neuroprotective barriers has since evolved to incorporate the neurovascular unit (NVU), the blood-cerebrospinal fluid (CSF) barrier, and the presence of CNS lymphatics that allow leukocyte egress. Identification of the cellular and molecular participants in BBB function at the NVU has allowed detailed analyses of mechanisms that contribute to BBB dysfunction in various disease states, which include both autoimmune and infectious etiologies. This chapter will introduce some of the cellular and molecular components that promote barrier function but may be manipulated by inflammatory mediators or pathogens during neuroinflammation or neuroinfectious diseases.

Structure and function of the blood-brain barrier

Frontiers in Pharmacology, 2010

Neural signalling within the central nervous system (CNS) requires a highly controlled microenvironment. Cells at three key interfaces form barriers between the blood and the CNS: the blood-brain barrier (BBB), blood-CSF barrier and the arachnoid barrier. The BBB at the level of brain microvessel endothelium is the major site of blood-CNS exchange. The structure and function of the BBB is summarised, the physical barrier formed by the endothelial tight junctions, and the transport barrier resulting from membrane transporters and vesicular mechanisms. The roles of associated cells are outlined, especially the endfeet of astrocytic glial cells, and pericytes and microglia. The embryonic development of the BBB, and changes in pathology are described. The BBB is subject to short and long-term regulation, which may be disturbed in pathology. Any programme for drug discovery or delivery, to target or avoid the CNS, needs to consider the special features of the BBB.

The blood-brain barrier in health and disease

Annals of Neurology, 2012

The blood-brain barrier (BBB) is a term used to describe a series of properties possessed by the vasculature of the central nervous system (CNS) that tightly regulate the movement of ions, molecules, and cells between the blood and the CNS. This barrier is crucial to provide the appropriate environment to allow for proper neural function, as well as protect the CNS from injury and disease. In this review, I discuss the cellular and molecular composition of the BBB and how the development and function of the BBB is regulated by interactions with the CNS microenvironment. I further discuss what is known about BBB dysfunction during CNS injury and disease, as well as methodology used to deliver drugs across the BBB to the CNS.

Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic Targets: An Overview

Pharmaceutics

The blood-brain barrier (BBB) is a fundamental component of the central nervous system (CNS). Its functional and structural integrity is vital to maintain the homeostasis of the brain microenvironment by controlling the passage of substances and regulating the trafficking of immune cells between the blood and the brain. The BBB is primarily composed of highly specialized microvascular endothelial cells. These cells’ special features and physiological properties are acquired and maintained through the concerted effort of hemodynamic and cellular cues from the surrounding environment. This complex multicellular system, comprising endothelial cells, astrocytes, pericytes, and neurons, is known as the neurovascular unit (NVU). The BBB strictly controls the transport of nutrients and metabolites into brain parenchyma through a tightly regulated transport system while limiting the access of potentially harmful substances via efflux transcytosis and metabolic mechanisms. Not surprisingly, ...

The blood-brain barrier/neurovascular unit in health and disease

Pharmacological reviews, 2005

The blood-brain barrier (BBB) is the regulated interface between the peripheral circulation and the central nervous system (CNS). Although originally observed by Paul Ehrlich in 1885, the nature of the BBB was debated well into the 20th century. The anatomical substrate of the BBB is the cerebral microvascular endothelium, which, together with astrocytes, pericytes, neurons, and the extracellular matrix, constitute a "neurovascular unit" that is essential for the health and function of the CNS. Tight junctions (TJ) between endothelial cells of the BBB restrict paracellular diffusion of water-soluble substances from blood to brain. The TJ is an intricate complex of transmembrane (junctional adhesion molecule-1, occludin, and claudins) and cytoplasmic (zonula occludens-1 and -2, cingulin, AF-6, and 7H6) proteins linked to the actin cytoskeleton. The expression and subcellular localization of TJ proteins are modulated by several intrinsic signaling pathways, including those i...

The role of the Blood-Brain Barrier in cellular communication: A review

World Journal of Biology Pharmacy and Health Sciences

The blood-brain barrier regulates the flow of ions, chemicals, and cells by acting as a conduit between blood and cerebral tissue. Additionally, it shields the brain against pathogen invasion and immune cell infiltration. It is composed of endothelial cells, pericytes, astrocytic end feet, perivascular macrophages, and microglial cells, which help in maintaining its integrity. There are various signaling pathways that are also involved in maintaining its integrity. The Wnt/β catenin, FZD4/FZD7, Hedgehog and TGF-β signaling pathways were evident to produce components or factors which stabilise the BBB. However, the NF-B and ERK signaling pathways caused the creation of MMPs, which increased the BBB's permeability. These functions are altered in pathological conditions like Alzheimer’s disease, and Parkinson’s disease which are also mentioned.

Looking at the blood–brain barrier: Molecular anatomy and possible investigation approaches

Brain Research Reviews, 2010

The blood-brain barrier (BBB) is a dynamic and complex interface between blood and the central nervous system that strictly controls the exchanges between the blood and brain compartments, therefore playing a key role in brain homeostasis and providing protection against many toxic compounds and pathogens. In this review, the unique properties of brain microvascular endothelial cells and intercellular junctions are examined. The specific interactions between endothelial cells and basement membrane as well as neighboring perivascular pericytes, glial cells and neurons, which altogether constitute the neurovascular unit and play an essential role in both health and function of the central nervous system, are also explored. Some relevant pathways across the endothelium, as well as mechanisms involved in the regulation of BBB permeability, and the emerging role of the BBB as a signaling interface are addressed as well. Furthermore, we summarize some of the experimental approaches that can be used to monitor BBB properties and function in a variety of conditions and have allowed recent advances in BBB knowledge. Elucidation of the molecular anatomy and dynamics of the BBB is an essential step for the development of new strategies directed to maintain or restore BBB integrity and barrier function and ultimately preserve the delicate interstitial brain environment.

The Blood Brain Barrier and Inflammation

Springer eBooks, 2017

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Mechanisms of blood-brain barrier breakdown

Neuroradiology, 1991

The functional status of the blood-brain barrier (BBB) must be taken into account when designing and interpreting brain imaging techniques. The integrity of the BBB is affected in many diseases of the brain, with the potential involvement of a number of different but poorly understood cellular mechanisms. Factors known to disrupt the BBB experimentally include arachidonic acid and the eicosanoids, bradykinin, histamine and free radicals. These active compounds, released in pathological tissue, may alter cytosolic calcium levels and induce second messenger systems leading to an alteration in BBB permeability. Extravasation of plasma proteins may occur via disrupted tight junctions, stimulation of fluid-phase vesicular transport or the formation of transcellular pores or channels.