Topic: brain endothelial cells

In previous studies, we identified low-perfused vascular abnormalities, termed “vascular scars”, surrounding A-beta plaques in Alzheimer's disease mouse models. We hypothesized that these vascular scars result from non-productive angiogenesis, a process in which total or partial reduction of the DLL4/NOTCH pathway leads to erratic angiogenesis and disassembly of vessels into non-conducting structures1. In this study, our objective was to investigate whether restoring the NOTCH pathway in brain endothelial cells could enhance vessel stability around A-beta plaques. To this aim, we injected the

The blood-brain barrier (BBB) separates the peripheral circulation from the brain. Brain endothelial cells (BECs) line the inner lumen of blood vessels in the brain and express tight junction proteins, that prevent the leakage of molecules between the cells into the brain, and efflux transporters that actively pump molecules out of the brain. As we age, the BBB becomes leaky and dysfunctional, leading to cerebrovascular diseases and dementia. We here investigated how BECs become senescent, a major feature of aging, and change their metabolic profile. First, we demonstrate that both the chemoth

Aims: Type 4 collagen encoded by COL4A1 gene is an integral component of blood-brain barrier (BBB). It has been reported that mutations in COL4A1 can cause various abnormalities in human cerebral microvasculature. We sought to determine the pathological consequences of COL4A1 deficiency in brain microvessels of adult mice. Methods: To knock out COL4A1 gene specifically in brain endothelial cells (BECs) of adult mice, we combined an adeno-associated virus to target the brain endothelium (AAV-BR1) with CRISPR/Cas9 system. The gRNA targeting exon 1 of COL4A1 was selected, packaged with AAV-BR1, a

Hypertension (HT) is a leading risk factor for brain injury. Endothelial dysfunction can be observed in HT and may result in blood-brain barrier (BBB) impairment, which leads to neuroinflammation. We aimed to assess the contribution of brain endothelial dysfunction to HT-induced brain injury in mice. We induced the loss of NEMO, the essential modulator of nuclear factor-κB, in brain endothelial cells (NemobeKO). Control mice received tamoxifen (NemoFl). HT was induced by chronic infusion of angiotensin II and nitric oxide synthase inhibitor in the drinking water for 28 days. After 7 days, HT m

Acute pancreatitis (AP) is an inflammatory gastroenterological disease, during which about 4% of all patients develop disturbance in consciousness. Besides this sypmtom among the severe AP cases 10 % show serious neurological involvement manifesting in pancreatic encephalopathy. Earlier research from our laboratory showed blood-brain barrier (BBB) permeability elevation in a rat non-invasive AP model. Now our goal was to identify potential BBB injury in pancreatitis patients. For this study we used serum from mild, moderate and severe AP patients to identify BBB opening by measuring neuron spe

Alzheimer's disease (AD) is a prevalent form of dementia, primarily affecting those aged 65 and older, known as late-onset or sporadic AD (sAD). It is characterized by the accumulation of βeta-amyloid protein aggregates and tau protein neurofibrillary tangles. Recent research highlights the crucial link between AD and dysfunction in the blood-brain barrier (BBB), primarily composed of brain endothelial cells (BECs), pericytes, and astrocytes, which regulate homeostasis in the brain. Transporter-mediated regulation at the BBB is pivotal, with dysregulation implicated in AD pathology. Non-invasi

The transcription factor Nrf2 (encoded by the Nfe2l2 gene) is a widely-expressed stress-responsive master regulator of several aspects of homeostatic physiology. Nrf2 plays a key role in preventing oxidative stress and inflammation. In the brain, Nrf2 is highly expressed by endothelial cells. Brain endothelial cells (BECs) are the key component of the blood brain barrier (BBB), which controls brain homeostasis. The role of BEC Nrf2 expression in maintaining homeostasis is not fully understood. In this project, through gain- and loss function experiments, we have found that Nrf2 activity in BEC

Alzheimer's disease (AD) is a significant global health challenge with no cure and limited treatment options. With the growing global ageing of the population and no effective treatment, AD incidence and prevalence are expected to double in Europe by 2050. The central clinical challenge remains developing a reliable, safe, and effective therapeutic option to halt disease progression and prevent cognitive failure. Understanding AD pathogenesis and identifying targets to prevent, halt, or cure it is a top priority for the global research and medical communities. Aiming to improve AD pathophysiol

This study aims to investigate the small extracellular vesicle (sEV) impact on the blood-brain barrier (BBB), particularly the interactions between sEVs and brain endothelial cells (BECs). The molecular components governing these interactions are currently unknown. In order to identify sEV-BEC interactors, a novel assay based on proximity-dependent biotinylation was developed. sEVs purified from a panel of cell lines derived from various peripheral and brain-derived tumors, including HEK293 embryonic kidney cells, SK-MEL-28 skin melanoma, A549 lung adenocarcinoma, MDA-MB-231 breast adenocarcin