Blood-brain barrier

…agents that can cross the blood brain barrier (BBB) and testing them clinically. Successful early-stage trials of new drugs from this NOFO would transition seamlessly to later stage trials using well-established NCI clinical trial mechanisms. To implement this concept, a highly collaborative GBM Therapeutics Network (GTN) of cross-cutting teams wi

…metabolism, memory, behavior, the blood-brain barrier, interactions with neurons and glia, and emerging therapeutic strategies.

…and inability to penetrate the blood-brain-barrier limit their use as potential therapeutics. To bypass these limitations, our research team has developed and patented small-sized, lipophilic

…in impaired blood flow, increased blood-brain barrier permeability and neuronal cell death. While small vessel disease is the leading cause of vascular dementia, the underlying mechanisms remain elusive, limiting treatment options. Visual stimulation at specific frequencies can enhance neuronal activity, leading to remodelling of the cerebrovascular architecture. Specifically, evoked gamma oscillations through stimulation at 40Hz has been shown to rescue motor and cogniti

…5xFAD (5xFAD;APN-/-) mice in terms of blood-brain barrier (BBB) permeabil

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

…impacting the permeability of the blood-brain barrier (BBB) and in par

…via efflux mediated transport at the blood-brain barrier (BBB). However

Periventricular leukomalacia (PVL) is a brain injury seen in preterm infants and causes a significant social, cultural, and economic burden by introducing permanent disabilities throughout life. Cognitive and motor impairments observed during the follow-up in cases with PVL limit their ability to participate in society. Colostrum milk, the first milk produced after birth, is a unique biological fluid. It is thought to have functions other than nutrition with its contents like microRNAs, extracellular vesicles, and neurotrophic mediators. Studies show that colostrum can be neuroprotective when

Astrocytes play an active role in shaping and maintaining neuronal circuits and the blood-brain barrier. In addition to their long-established role in extracellular potassium buffering and glutamate uptake, these cells can also regulate the activity of local synaptic circuits through secretion and clearance of neurotransmitters. Whilst the molecular signal exchange between astroglia and synapses occurs in a highly heterogeneous microenvironment on the nanoscale, the spatial subcellular distribution of the underlying molecular machineries remains poorly understood. Similarly, in addition to clo

There is increasing evidence for dysfunction of blood-brain barrier (BBB) to play a critical role in the pathological mechanisms and progression of Parkinson’s disease (PD). PD-related pathology such as alpha-synuclein (aSyn) accumulation potentially affects the integrity of the BBB starting at an early disease stage. This could result in a self-perpetuating pathophysiology of inflammation and BBB alteration, which contributes to neurodegeneration.In our initial study, we described microvascular changes during disease progression in a mouse model with overexpression of human aSyn (Thy1-aSyn, l

…endothelial cells that form a tight blood-brain barrier (BBB). Weakening of the junctional proteins can lead to BBB disruption. This can have detrimental effects on patients’ health, as the homeostatic environment of the brain becomes compromised.The MIMETAS OrganoPlate® is a microfluidic platform that enables perfused, 3D culture of up to 96 tissues in parallel in a membrane-free manner. The microfluidic channels allow growth of perfused tubular endothelial structures. Furthermore, the system allows for automation, enabling higher through

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

…into the brain is hampered by the blood-brain barrier. Small antibody fragment from camelids, called Nanobody®, are good alternative to these conventional antibodies. In the present work, we study how brain-penetrating nanobodies reach the brain after peripheral administration in mice by developping different approaches. We used nanobodies specific to a metabotropic glutamate (mGlu) receptor, the mGlu2 subtype, as a model. F

…species followed by leakage of the blood-brain barrier and neurotoxicity. Transient neuroinflammation is understood to be largely protective, chronic neuroinflammation, however, contributes to the pathology of Alzheimer’s disease, traumatic brain injury, and many more. In this study, we focus on the aspect of cytokine-induced neuroinflammation in human microglia cells and especially in astrocytes, since many studies on

…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

…cross biological membranes like the blood-brain barrier. They are being used as drug carrier systems and have attracted attention recently. In AD and similar diseases, exposure to oxidant molecules increases in

The blood-brain barrier (BBB) protects the brain and provides oxygen and nutrients for the central nervous system (CNS), but it also restricts the entry of pharmaceutical drugs into the brain. Cell culture models are essential to investigate cerebral drug delivery. Microfluidic chip devices allow complex and physiological modelling of the BBB. Induced pluripotent stem cell (iPSC) based technologies, the formation and use of human brain organoids provide simplified 3D modeling. Our aim was to (1) create and optimize a new, dynamic cell culture lab-on-a-chip model by the co-culture of a BBB mode

…in blood, and ability to cross the blood-brain barrier make them promising biomarker candidates for diagnosing central nervous system (CNS) disorders. However, further characterization of miRNA biomarkers is needed to identify key factors for diagnosing CNS disorders. In this study, we aimed to detect and characterize a differentially expressed miRNA as a biomarker for Major Depressive Disorder (MDD). We performed RNA sequencing o

…neurodegeneration, neuroinflammation, blood-brain barrier (BBB) integrity, cerebral glucose metabolism, and neurodegenerative progression

Recent findings reveal an increased risk of cognitive impairment in individuals with chronic kidney disease (CKD). To better understand the interactions between CKD and neurodegenerative diseases, twenty Sprague Dawley rats underwent either 5/6 Nephrectomy (Nx) or Sham operation through random allocation at two different time onsets: six or twelve weeks of age. Twenty-four weeks after surgery, renal function and histopathological parameters were evaluated. The 5/6Nx rats showed increased blood creatinine and urea levels as well as kidney inflammation at both time onsets. This renal damage appe

…In ICH, disruption of blood-brain barrier followed by infiltration of copper from plasma into brain, results in copper overload and cuproptosis. Oligomerization of Dihydrolipoamide S-Acetyltransferase (DLAT) has been identified as a hallmark of cuproptosis. We aim to study whether ICH would induce cuproptosis as a result of DLAT accumulation. ICH was induced in C57BL/6 mice by c

…is a great challenge because of the blood-brain barrier selectivity. However, nanoliposomal systems can provide an alternative to this drawback. This study aimed to design and develop nanoliposomes based on soy lecithin loaded with galantamine (acetylcholinesterase inhibitor) or DNA aptamers designed to hinder the aggregation of proteins like Aβ, TDP-43 and α-synuclein. For this, a complete physicochemical characterization of soy lecithin and other raw materials was carried

…circulating stem cells must cross the blood-brain barrier (BBB) and might get trapped in peripheral organs, resulting in an insufficient number of cells reaching the lesion. To optimize their migration across the BBB, we aimed to mimic immune cells as they extravasate into the brain parenchyma following injury. For in