Chapter 10 Vascular endothelium and the blood–brain barrier

ABSTRACTThe Gram-positive bacteriumStreptococcus pneumoniaeis the main causative agent of bacterial meningitis.S. pneumoniaeis thought to invade the central nervous system via the bloodstream by crossing the vascular endothelium of the blood-brain barrier. The exact mechanism by which pneumococci cross endothelial cell barriers before meningitis develops is unknown. Here, we investigated the role of PECAM-1/CD31, one of the major endothelial cell adhesion molecules, inS. pneumoniaeadhesion to vascular endothelium of the blood-brain barrier. Mice were intravenously infected with pneumococci and sacrificed at various time points to represent stages preceding meningitis. Immunofluorescent analysis of brain tissue of infected mice showed that pneumococci colocalized with PECAM-1. In human brain microvascular endothelial cells (HBMEC) incubated withS. pneumoniae, we observed a clear colocalization between PECAM-1 and pneumococci. Blocking of PECAM-1 reduced the adhesion ofS. pneumoniaeto endothelial cellsin vitro, implying that PECAM-1 is involved in pneumococcal adhesion to the cells. Furthermore, using endothelial cell protein lysates, we demonstrated thatS. pneumoniaephysically binds to PECAM-1. Moreover, bothin vitroandin vivoPECAM-1 colocalizes with theS. pneumoniaeadhesion receptor pIgR. Lastly, immunoprecipitation experiments revealed that PECAM-1 can physically interact with pIgR. In summary, we show for the first time that blood-borneS. pneumoniaecolocalizes with PECAM-1 expressed by brain microvascular endothelium and that, in addition, they colocalize with pIgR. We hypothesize that this interaction plays a role in pneumococcal binding to the blood-brain barrier vasculature prior to invasion into the brain.

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Posterior Reversible Encephalopathy Syndrome as Presenting Form of Very Early Systemic Sclerosis

Case Reports in Neurological Medicine ◽

10.1155/2015/290378 ◽

2015 ◽

Vol 2015 ◽

pp. 1-3

Author(s):

María Isabel Pedraza ◽

Julia Barbado ◽

Marina Ruiz ◽

Ángel Luis Guerrero

Keyword(s):

Systemic Sclerosis ◽

Arterial Hypertension ◽

Blood Brain Barrier ◽

Posterior Reversible Encephalopathy Syndrome ◽

Vascular Endothelium ◽

Brain Barrier ◽

Posterior Reversible Encephalopathy ◽

Blood Brain ◽

Reversible Encephalopathy ◽

Early Systemic Sclerosis

Introduction. Posterior Reversible Encephalopathy Syndrome (PRES) is an increasingly recognized clinical and radiological entity with a wide spectrum of symptoms. Its mechanism depends on failure of the blood-brain barrier due to high systemic blood pressure (BP) and loss of integrity of vascular endothelium related with different triggers.Methods. We aim to report a case of PRES induced by arterial hypertension and very early systemic sclerosis (SSc) not previously known.Results. A 64-year-old female was admitted due to 1-week pulsating headache more prominent on frontal scalp, accompanied by phonophobia, photophobia, and facial flushing. Neurological exam revealed brisk deep tendon reflex. Brain magnetic resonance imaging (MRI) showed subcortical lesions mainly located in posterior regions. BP was monitored and episodic arterial hypertension was detected. In laboratory tests positive anti-topoisomerase I antibodies were detected. BP was controlled with angiotensin-converting-enzyme inhibitors and headache improved. In a new MRI a month later improvement of white matter lesions was observed. Capillaroscopy showed “active pattern,” considered typical of SSc.Conclusion. In SSc anti-endothelial cell antibodies impair vascular endothelium and liberation of vasoconstrictors leads to BP increasing and disruption of blood-brain barrier autoregulation mechanisms. PRES can be the first manifestation of very early SSc and this entity should be considered even in absence of skin lesions or Raynaud phenomenon.

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A novel epigenetic marker, TET2, is identified in the intractable epileptic brain and regulates ABCB1 in the blood-brain barrier

10.21203/rs.3.rs-676547/v1 ◽

2021 ◽

Author(s):

Fancheng Kong ◽

Li-Qin Lang ◽

Xia-Ling Zhang ◽

Ming-Kang Zhong ◽

Chun-Lai Ma

Keyword(s):

Blood Brain Barrier ◽

Vascular Endothelium ◽

Hippocampal Sclerosis ◽

Expression Patterns ◽

Temporal Cortex ◽

Brain Barrier ◽

Brain Vessels ◽

Blood Brain ◽

Epigenetic Marker ◽

Regulatory Effects

Abstract BackgroundDrug-resistant epilepsy (DRE) is a chronic condition derived from spontaneous changes and regulatory effects in the epileptic brain. DNA methylation, an inheritable but reversible epigenetic change, may participate in this complicated regulatory network. As demethylation factors, ten-eleven translocation (TET) family members have become a focus in recent studies of neurological disorders. Thus, we aimed to unravel their role in DRE and their function related to the possible refractory factor ABCB1 in a blood-brain barrier (BBB) model.MethodsWe quantified and localized TET1, TET2 and 5-hydroxymethylcytosine (5-hmC) in the temporal lobe cortex of DRE patients (n = 27) and traumatic brain haemorrhage controls (n = 10) by immunochemical staining. TET2 and ABCB1 expression patterns were determined in the temporal cortex and isolated brain capillaries of DRE patients using immunohistological detection and Western blot analysis, respectively. A BBB model constructed with hCMEC/D3 cells was used to verify the demethylation and regulatory effects of TET2 on ABCB1.ResultsTET2 expression was significantly increased in the temporal cortical tissue of DRE patients with or without hippocampal sclerosis (HS) compared to control patients, while TET1 and 5-hmC showed differences in expression. We also discovered that the vascular endothelium of DRE patients has a strong affinity for TET2. ABCB1 and TET2 have identical densities in the DRE temporal cortex, and they both have evidently higher expression in the vascular endothelium from the neocortex of DRE patients. In the BBB, TET2 depletion can cause attenuated expression and function of ABCB1, as well as a pattern of higher methylation in CpG islands of the ABCB1 promoter.ConclusionsThrough a cohort study performed on the temporal cortex and brain vessels of DRE patients, we identified a novel epigenetic marker, TET2. Data from experiments in a BBB model suggest that TET2 has a specific regulatory effect on ABCB1, which may serve as a potential mechanism and target in DRE and requires further research.

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