The blood–brain barrier: an overview

Ballabh, Praveen; Braun, Alex; Nedergaard, Maiken

doi:10.1016/j.nbd.2003.12.016

Cited by 1,896 publications

(750 citation statements)

References 120 publications

Supporting

Mentioning

735

Contrasting

Unclassified

Order By: Relevance

“…It is probable, therefore, that epinephrine causes selective leaks of the BBB in the amygdala. A region-specific abrogation of the barrier might also occur if receptors for epinephrine are differentially expressed throughout the cerebral vasculature, with more epinephrine receptors present on vessels in the amygdala (30).…”

Section: Discussionmentioning

confidence: 99%

Immunity and behavior: Antibodies alter emotion

Huerta

Kowal

DeGiorgio

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

258

226

View full text Add to dashboard Cite

Systemic lupus erythematosus is an autoimmune disease in which most patients express Abs that bind double-stranded DNA. Recent work has shown that a subset of lupus Abs can crossreact with the NR2A and NR2B subunits of the NMDA receptor. This receptor is expressed in neurons throughout the brain but is at highest density within cells of the hippocampus, amygdala, and hypothalamus. The neurons in the CNS are normally protected from brain-reactive Abs by the blood-brain barrier (BBB); however, a breach in the barrier's integrity exposes neurons to potentially pathogenic Abs. Previously, we have shown that mice that are immunized with a peptide mimetope of DNA produce lupus-like Abs that crossreact with DNA and the NMDA receptor. Moreover, after abrogation of the BBB by treatment with lipopolysaccharide, the immunized mice display hippocampal neuron damage with ensuing memory impairment. Given that rises in epinephrine can increase cerebral blood flow and can cause leaks in the BBB, we decided to investigate whether epinephrine could act as a permissive agent for Ab-mediated neurotoxicity. Here, we show that peptide-immunized mice, given epinephrine to open the BBB, lose neurons in the lateral amygdala and develop a behavioral disorder characterized by a deficient response to fear-conditioning paradigms. Thus, the agent used to open the BBB determines which brain region is made vulnerable to neurotoxic Abs, and Abs that penetrate brain tissue can cause changes not only in cognitive competence, but also in emotional behavior.amygdala ͉ anti-NMDA receptor antibody ͉ anti-DNA antibody ͉ fear conditioning ͉ systemic lupus erythematosus

show abstract

Section: Discussionmentioning

confidence: 99%

Immunity and behavior: Antibodies alter emotion

Huerta

Kowal

DeGiorgio

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

258

226

View full text Add to dashboard Cite

show abstract

“…Passive diffusion through the BBB is regulated by brain endothelial tight junctions (TJs), which are composed of transmembrane and cytosolic TJ‐associated protein complexes 1, 2. Among major TJ proteins, which play a critical role in the formation and integrity of vascular barrier are occludin, claudins (claudin‐5 [CLDN5] and claudin‐1 [CLDN1], among other family members), and a major scaffolding protein ZO‐1 (member of the zonula occludens protein family) 3, 4.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of MicroRNA‐155 Supports Endothelial Tight Junction Integrity Following Oxygen‐Glucose Deprivation

Peña-Philippides

Gardiner

Caballero-Garrido

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundBrain microvascular endothelial cells form a highly selective blood brain barrier regulated by the endothelial tight junctions. Cerebral ischemia selectively targets tight junction protein complexes, which leads to significant damage to cerebral microvasculature. Short noncoding molecules called microRNAs are implicated in the regulation of various pathological states, including endothelial barrier dysfunction. In the present study, we investigated the influence of microRNA‐155 (miR‐155) on the barrier characteristics of human primary brain microvascular endothelial cells (HBMECs).Methods and ResultsOxygen‐glucose deprivation was used as an in vitro model of ischemic stroke. HBMECs were subjected to 3 hours of oxygen‐glucose deprivation, followed by transfections with miR‐155 inhibitor, mimic, or appropriate control oligonucleotides. Intact normoxia control HBMECs and 4 oxygen‐glucose deprivation–treated groups of cells transfected with appropriate nucleotide were subjected to endothelial monolayer electrical resistance and permeability assays, cell viability assay, assessment of NO and human cytokine/chemokine release, immunofluorescence microscopy, Western blot, and polymerase chain reaction analyses. Assessment of endothelial resistance and permeability demonstrated that miR‐155 inhibition improved HBMECs monolayer integrity. In addition, miR‐155 inhibition significantly increased the levels of major tight junction proteins claudin‐1 and zonula occludens protein‐1, while its overexpression reduced these levels. Immunoprecipitation and colocalization analyses detected that miR‐155 inhibition supported the association between zonula occludens protein‐1 and claudin‐1 and their stabilization at the HBMEC membrane. Luciferase reporter assay verified that claudin‐1 is directly targeted by miR‐155.ConclusionsBased on these results, we conclude that miR‐155 inhibition–induced strengthening of endothelial tight junctions after oxygen‐glucose deprivation is mediated via its direct target protein claudin‐1.

show abstract

“…The BBB is a major physical and physiological barrier that regulates the passage of solute, macromolecules, and cells from the circulation into the brain interstitial fluid. It is formed mainly by the intercellular tight junctions of the brain microvascular endothelial cells [14,15]. The commonly accepted theory proposes that an increase in blood pressure above the autoregulatory capacity of the cerebral circulation successively results in cerebral hyperperfusion via arteriolar dilation, leading to cerebral endothelial damage, loss of BBB integrity, and fluid and protein extravasation.…”

Section: Discussionmentioning

confidence: 99%

An atypical subacute presentation of posterior reversible encephalopathy syndrome

Bazuaye-Ekwuyasi

Chow

Schmalzle

2017

Journal of Community Hospital Internal Medicine Perspectives

View full text Add to dashboard Cite

Posterior reversible encephalopathy syndrome (PRES) characteristically presents with rapid onset of headache, seizure, encephalopathy, and visual changes, along with evidence of parieto-occipital vasogenic edema on magnetic resonance imaging. We describe the case of a 41-year-old female with a protracted presentation of two of the four classic PRES symptoms, which were not immediately recognized as PRES due to the presence of multiple other comorbidities and reasons for encephalopathy. This case highlights the possibility of atypical presentations of PRES and the diagnostic challenges in making this clinical diagnosis when competing diagnoses are present.

show abstract

The blood–brain barrier: an overview

Cited by 1,896 publications

References 120 publications

Immunity and behavior: Antibodies alter emotion

Immunity and behavior: Antibodies alter emotion

Inhibition of MicroRNA‐155 Supports Endothelial Tight Junction Integrity Following Oxygen‐Glucose Deprivation

An atypical subacute presentation of posterior reversible encephalopathy syndrome

Contact Info

Product

Resources

About