Cells of the Blood–Brain Barrier: An Overview of the Neurovascular Unit in Health and Disease

McConnell, Heather L.; Mishra, Anusha

doi:10.1007/978-1-0716-2289-6_1

Cited by 38 publications

(29 citation statements)

References 164 publications

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“…The neurovascular unit (NVU) of the BBB is composed of brain microvascular endothelial cells, pericytes, and astrocytes [ 46 , 47 ]. Tight junction (TJ) proteins link endothelial cells together and form a selective permeable barrier between the blood and the CNS, which prevents toxic molecules, viruses, bacteria, and inflammatory cells from reaching the brain [ 34 , 48 ].…”

Section: Pericytes and Brain Infection By Hiv-1mentioning

confidence: 99%

Pericyte infection by HIV-1: a fatal attraction

et al. 2022

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While HIV-1 is primarily an infection of CD4 + T cells, there is an emerging interest towards understanding how infection of other cell types can contribute to HIV-associated comorbidities. For HIV-1 to cross from the blood stream into tissues, the virus must come in direct contact with the vascular endothelium, including pericytes that envelope vascular endothelial cells. Pericytes are multifunctional cells that have been recognized for their essential role in angiogenesis, vessel maintenance, and blood flow rate. Most importantly, recent evidence has shown that pericytes can be a target of HIV-1 infection and support an active stage of the viral life cycle, with latency also suggested by in vitro data. Pericyte infection by HIV-1 has been confirmed in the postmortem human brains and in lungs from SIV-infected macaques. Moreover, pericyte dysfunction has been implicated in a variety of pathologies ranging from ischemic stroke to diabetes, which are common comorbidities among people with HIV-1. In this review, we discuss the role of pericytes during HIV-1 infection and their contribution to the progression of HIV-associated comorbidities.

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Section: Pericytes and Brain Infection By Hiv-1mentioning

confidence: 99%

Pericyte infection by HIV-1: a fatal attraction

et al. 2022

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“…The neurovascular unit is composed of various interacting cells, including neurons, astrocytes, microglia, pericytes, endothelial cells, and vascular smooth muscle cells ( 29 ). Neurovascular unit components interact and balance microenvironments, thereby ensuring stable neuronal function ( 30 ). HIF-1α is extensively expressed in the neurovascular unit and mediates the transcriptional expression of more than 100 genes under hypoxic conditions ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Potential role of serum hypoxia-inducible factor 1alpha as a biomarker of delayed cerebral ischemia and poor clinical outcome after human aneurysmal subarachnoid hemorrhage: A prospective, longitudinal, multicenter, and observational study

et al. 2022

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ObjectiveHypoxia-inducible factor 1alpha (HIF-1α) functions as a crucial transcriptional mediator in hypoxic and ischemic brain response. We endeavored to assess the prognostic significance of serum HIF-1α in human aneurysmal subarachnoid hemorrhage (aSAH).MethodsIn this prospective, longitudinal, multicenter, and observational study of 257 patients with aSAH and 100 healthy controls, serum HIF-1α levels were quantified. Univariate analyses, followed by multivariate analyses, were performed to discern the relationship between serum HIF-1α levels and severity and delayed cerebral ischemia (DCI) plus poststroke 6-month poor outcome [extended Glasgow outcome scale (GOSE) scores of 1–4]. Predictive efficiency was determined under the receiver operating characteristic (ROC) curve.ResultsThere were significantly increased serum HIF-lα levels after aSAH, in comparison to controls (median, 288.0 vs. 102.6 pg/ml; P < 0.001). Serum HIF-lα levels were independently correlated with Hunt–Hess scores [β, 78.376; 95% confidence interval (CI): 56.446–100.305; P = 0.001] and modified Fisher scores (β, 52.037; 95% CI: 23.461–80.614; P = 0.002). Serum HIF-lα levels displayed significant efficiency for discriminating DCI risk [area under ROC curve (AUC), 0.751; 95% CI: 0.687–0.815; P < 0.001] and poor outcome (AUC, 0.791; 95% CI: 0.736–0.846; P < 0.001). Using the Youden method, serum HIF-1α levels >229.3 pg/ml predicted the development of DCI with 92.3% sensitivity and 48.4% specificity and serum HIF-1α levels >384.0 pg/ml differentiated the risk of a poor prognosis with 71.4% sensitivity and 81.1% specificity. Serum HIF-1α levels >229.3 pg/ml were independently predictive of DCI [odds ratio (OR), 3.061; 95% CI: 1.045–8.965; P = 0.041] and serum HIF-1α levels >384.0 pg/ml were independently associated with a poor outcome (OR, 2.907; 95% CI: 1.403–6.024; P = 0.004). The DCI predictive ability of their combination was significantly superior to those of Hunt–Hess scores (AUC, 0.800; 95% CI: 0.745–0.855; P = 0.039) and modified Fisher scores (AUC, 0.784; 95% CI: 0.726–0.843; P = 0.004). The prognostic predictive ability of their combination substantially exceeded those of Hunt–Hess scores (AUC, 0.839; 95% CI: 0.791–0.886; P < 0.001) and modified Fisher scores (AUC, 0.844; 95% CI: 0.799–0.890; P < 0.001).ConclusionElevated serum HIF-lα levels after aSAH, in independent correlation with stroke severity, were independently associated with DCI and 6-month poor outcome, substantializing serum HIF-lα as a potential prognostic biomarker of aSAH.

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“…• Continuous monolayer of ECs that are tightly connected via transmembrane tight junction proteins (3,6,7) • ↑ Mfsda2 expression, ↓ transcytosis (8-10)…”

Section: Endothelial Cellsmentioning

confidence: 99%

Addressing blood-brain-tumor-barrier heterogeneity in pediatric brain tumors with innovative preclinical models

et al. 2023

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Brain tumors represent the leading cause of disease-related mortality and morbidity in children, with effective treatments urgently required. One factor limiting the effectiveness of systemic therapy is the blood-brain-barrier (BBB), which limits the brain penetration of many anticancer drugs. BBB integrity is often compromised in tumors, referred to as the blood-brain-tumor-barrier (BBTB), and the impact of a compromised BBTB on the therapeutic sensitivity of brain tumors has been clearly shown for a few selected agents. However, the heterogeneity of barrier alteration observed within a single tumor and across distinct pediatric tumor types represents an additional challenge. Herein, we discuss what is known regarding the heterogeneity of tumor-associated vasculature in pediatric brain tumors. We discuss innovative and complementary preclinical model systems that will facilitate real-time functional analyses of BBTB for all pediatric brain tumor types. We believe a broader use of these preclinical models will enable us to develop a greater understanding of the processes underlying tumor-associated vasculature formation and ultimately more efficacious treatment options.

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Cells of the Blood–Brain Barrier: An Overview of the Neurovascular Unit in Health and Disease

Cited by 38 publications

References 164 publications

Pericyte infection by HIV-1: a fatal attraction

Pericyte infection by HIV-1: a fatal attraction

Potential role of serum hypoxia-inducible factor 1alpha as a biomarker of delayed cerebral ischemia and poor clinical outcome after human aneurysmal subarachnoid hemorrhage: A prospective, longitudinal, multicenter, and observational study

Addressing blood-brain-tumor-barrier heterogeneity in pediatric brain tumors with innovative preclinical models

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