Blood Brain Barrier

BBB is a separation of circulating blood and CSF in the CNS and protects the CNS
tissues from circulating cells and factors (Pachter et al., 2003).

From: Advances in Virus Research, 2011

Related terms:

Neoplasm, Tight Junction, Serositis, Protein, Central Nervous System, Nanoparti-

cle, Cerebrospinal Fluid, Astrocyte

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Multimodality Targeting of Glioma

Cells
Zhenqiang He MD, ... Yi Fan MD, PhD, in Glioblastoma, 2016

Blood-brain barrier
The BBB is an anatomic and biochemical barrier that protects the brain from
potentially harmful substances. The BBB ECs are characterized by the absence of
fenestrations, more extensive tight junctions, and sparse pinocytic vesicular trans-
port. EC tight junctions limit the paracellular flux of hydrophilic molecules across the
BBB. Although disruption of the BBB can be found in most patients with GBM, there
are still regions of the tumor with an intact BBB.168 Most lipophilic small-molecule
inhibitors are thought to be able to penetrate the BBB by passive diffusion, but tight
junctions hold the ECs together on the BBB and limit the delivery of targeted agents
into the tumor.168,169

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Pathophysiology of Ischemia-Reperfu-
sion Injury and Hemorrhagic Transfor-
mation in the Brain
Z. Yu, ... X. Wang, in Primer on Cerebrovascular Diseases (Second Edition), 2017

Blood–Brain-Barrier Disruption
BBB disruption is a consequence of aforementioned reperfusion-injury mechanisms
including oxidative stress, leukocyte infiltration, platelet activation, and complement
activation. It has been documented by both animal studies and clinical investigation
that BBB disruption occurs during cerebral reperfusion and can lead to vascular
edema and HT. Previous studies have reported that BBB disruption occurs after 3 h
of reperfusion following transient occlusion, whereas BBB remained intact after 6-h
occlusion in a permanent occlusion group. A clinical study involving 144 patients
with acute stroke showed that BBB disruption was more common in patients with
reperfusion than in those without reperfusion. In addition, in the reperfused group,
patients with BBB disruption were more likely to have a poorer clinical outcome
than those without disruption [6]. This study established the association of early BBB
disruption with HT and poor clinical outcome in humans.

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Diseases Mediated by the BBB

William A. Banks, in Handbook of Biologically Active Peptides (Second Edition), 2013

Summary
The BBB is pivotal in an endocrine-like communication between the CNS and
peripheral tissues. The BBB does this by regulating the exchange of information
molecules such as peptides and proteins between the CNS and peripheral tissues.
When the BBB does not perform this function correctly, diseases can occur. Here,
five examples of BBB dysfunction and associated diseases were discussed. In most
of these cases, the exact magnitude of the contribution of BBB dysfunction to the
overall disease process is not established. However, these examples serve to illustrate
the concept that the BBB is intimately involved in the onset and promotion of disease
processes.

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Role of Inflammation in Environmen-

tal Neurotoxicity
Tamara L. Young, ... Matthew J. Campen, in Advances in Neurotoxicology, 2019

Abstract
The blood-brain barrier (BBB) is a highly selective membrane barrier at the brain
microvessel level that facilitates transport between the systemic circulation and the
central nervous system. A growing body of evidence supports a major role for the
BBB in the etiology and pathogenesis of multiple vascular and neurodegenerative
disorders. Recently, an appreciation for the impact of air pollution exposures on
neurological function has emerged. The BBB may serve as an intermediary between
environmental agents and downstream neurological consequences. This review de-
scribes the structure and function of the BBB and its involvement in metabolic, vas-
cular, and neurodegenerative diseases such as diabetes mellitus, stroke, Alzheimer's
disease, and multiple sclerosis. The relationship between neuroinflammation and
BBB disruption is examined, and a possible role for the BBB in air pollution expo-
sure-associated neurological impairments is discussed. Commonly used clinical and
preclinical methods to detect BBB permeability are described as are animal models
used to study BBB breakdown. Finally, open questions concerning the impact of
environmental stressors on the BBB are explored and current approaches aimed at
altering BBB integrity to enhance pharmaceutical uptake into the CNS are discussed.

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Pharmacology of the Blood Brain Barri-

er: Targeting CNS Disorders
Martha E. O’Donnell, in Advances in Pharmacology, 2014

Abstract
Blood–brain barrier (BBB) endothelial cells form a barrier that is highly restrictive to
passage of solutes between blood and brain. Many BBB transport mechanisms have
been described that mediate transcellular movement of solutes across the barrier
either into or out of the brain. One class of BBB transporters that is all too often
overlooked is that of the ion transporters. The BBB has a rich array of ion transporters
and channels that carry Na, K, Cl, HCO3, Ca, and other ions. Many of these are
asymmetrically distributed between the luminal and abluminal membranes, giving
BBB endothelial cells the ability to perform vectorial transport of ions across the
barrier between blood and brain. In this manner, the BBB performs the impor-
tant function of regulating the volume and composition of brain interstitial fluid.
Through functional coupling of luminal and abluminal transporters and channels,
the BBB carries Na, Cl, and other ions from blood into brain, producing up to 30% of
brain interstitial fluid in healthy brain. During ischemic stroke cerebral edema forms
by processes involving increased activity of BBB luminal Na transporters, resulting
in “hypersecretion” of Na, Cl, and water into the brain interstitium. This review
discusses the roles of luminal BBB Na transporters in edema formation in stroke,
with an emphasis on Na–K–Cl cotransport and Na/H exchange. Evidence that these
transporters provide effective therapeutic targets for reduction of edema in stroke is
also discussed, as are recent findings regarding signaling pathways responsible for
ischemia stimulation of the BBB Na transporters.

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Nanotherapeutic Approach to Target-

ing HIV-1 in the CNS
Supriya D. Mahajan, ... Stanley A. Schwartz, in Nanotechnology in Diagnosis, Treat-
ment and Prophylaxis of Infectious Diseases, 2015

15.5 The Blood–Brain Barrier

The BBB is a critical interface. It acts as a physical and metabolic barrier between
the CNS and the peripheral circulation that serves to regulate and protect the mi-
croenvironment of the brain. The primary function of the normal BBB is to establish
and maintain homeostasis in the CNS (Bradbury, 1993). The BBB is not rigid and
comprises dynamic vessels that are capable of responding to rapid changes in the
brain or blood. The BBB is composed of specialized brain capillary endothelial cells
and astrocytic end feet that enhance the differentiation of the BBB endothelium. The
BBB is composed of at least three types of cell-to-cell junctional structures between
adjacent endothelial cells and/or between endothelial cells and astrocytes, the gap
junctions, adherens junction, and the TJs. The high expression of TJ proteins is a
special characteristic of the BBB.

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INFLAMMATION | Modulation of Neu-

ronal Excitability: Vascular Changes
and Inflammation
P.F. Fabene, ... M. Bentivoglio, in Encyclopedia of Basic Epilepsy Research, 2009

Blood–Brain Barrier
The BBB is a selective barrier formed by tight junctions between endothelial cells,
acting primarily to limiting the penetration of different substances from the blood
into the brain. The BBB presents a ‘physical barrier,’ which forces most molecular
traffic to take a transcellular route across the BBB, rather than moving paracellularly
through the junctions. The high density of the tight junctions that compose the
BBB restricts the passage of substances from the bloodstream much more than
endothelial cells in capillaries elsewhere in the body. Astrocyte cell processes, called
‘end-feet,’ surround the endothelial cells of the BBB (forming the so-called glia
limitans), providing biochemical support to the endothelial cells. BBB disruption is
associated with various neurological disorders. During the past years, there has been
increasing interest in BBB alterations in epilepsy, both in humans and in animal
studies.

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Microfluidics in Cell Biology Part A: Mi-

crofluidics for Multicellular Systems
Eunice Chin, Eyleen Goh, in Methods in Cell Biology, 2018

Abstract
The blood–brain barrier (BBB) plays a vital role in the maintenance of brain home-
ostasis. It strictly restricts the passage of molecules from the brain vasculature into
the brain via its high transendothelial electrical resistance and low paracellular and
transcellular permeability. Specialized brain endothelial cells, astrocytes, pericytes,
neurons, and microglia contribute synergistically to the functional properties of the
BBB. Because of its complexity and relative inaccessibility, BBB research is fraught
with difficulties. Most studies rely on animal or cell culture models, which are not
able to fully recapitulate the properties of the human BBB. The recent development
of three-dimensional (3D) microfluidic models of the BBB could address this issue.
This chapter aims to provide an overview of the recent advances in modeling the
BBB on microdevices, and illustrate important considerations for the design of such
models. In addition, protocols for the fabrication of a 3D BBB microfluidic chip
and BBB assessment experiments, including immunocytochemistry for analyzing
cell morphology and protein marker expression, permeability assay, and calcium
imaging for studying neuronal function as a measure of BBB integrity, are presented
here. It is envisioned that continued advancements in microtechnology can lead to
the creation of realistic in vivo-like BBB-on-chip models.

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Blood–Brain Barrier Disruption

Jacqueline A. Hubbard, Devin K. Binder, in Astrocytes and Epilepsy, 2016

Overview
The blood–brain barrier (BBB) is a dynamic system that separates the peripheral
blood from the neural tissue. It is composed of endothelial cells connected through
gap junctional proteins and works together with various other cell types to create a
unique microenvironment for proper neuronal function. BBB disruption, however,
has been implicated in epilepsy. Various studies have demonstrated increased BBB
permeability and albumin extravasation into the brain after prolonged seizures.
Disruption of the BBB or direct application of serum albumin to the brain itself may
also be sufficient to cause hyperexcitability. More recent research has focused on
deciphering the mechanism of BBB dysfunction in the pathogenesis of epilepsy and
several studies have suggested the involvement of the inflammatory transforming
growth factor (TGF- ) pathway. This chapter will review the current evidence for the
involvement of BBB disruption in epileptogenesis and will also consider the clinical
relevance of early detection of BBB damage.

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Anatomy and physiology of

blood-brain barrier
Smriti Gupta, ... Rajat Sandhir, in Brain Targeted Drug Delivery System, 2019

Abstract
Blood-brain barrier (BBB) is an anatomical gateway that is an essential requisite for
maintenance of homeostasis and physiological environment of the central nervous
system (CNS). It is a distinctive interface between CNS and peripheral circulation that
strictly regulates the entry of specific molecules from circulation or their clearance.
The functional unit of BBB is neurovascular unit, which includes specialized en-
 dothelial cells, astrocytes, pericytes, and neurons along with extracellular matrix. The
tight junction is an intricate complex of transmembrane (junctional adhesion mole-
cule-1, occludin, and claudins) and cytoplasmic (zonula occludens-1 and occludin-2)
proteins between the endothelial cells that are responsible for the barrier function
of BBB. Specific transporters exist at the BBB for movement of various nutrients,
ions, organic anions, and macromolecules. Therefore, alterations in structure and
function of BBB in disease can be detrimental to CNS functions.

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