Search results for " Barrier"
showing 10 items of 540 documents
Aquaporins and Brain Tumors
2016
Brain primary tumors are among the most diverse and complex human cancers, and they are normally classified on the basis of the cell-type and/or the grade of malignancy (the most malignant being glioblastoma multiforme (GBM), grade IV). Glioma cells are able to migrate throughout the brain and to stimulate angiogenesis, by inducing brain capillary endothelial cell proliferation. This in turn causes loss of tight junctions and fragility of the blood–brain barrier, which becomes leaky. As a consequence, the most serious clinical complication of glioblastoma is the vasogenic brain edema. Both glioma cell migration and edema have been correlated with modification of the expression/localization …
A Novel Cervical Spinal Cord Window Preparation Allows for Two-Photon Imaging of T-Cell Interactions with the Cervical Spinal Cord Microvasculature d…
2017
T-cell migration across the blood-brain barrier (BBB) is a crucial step in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple scle rosis (MS). Two-photon intravital microscopy (2P-IVM) has been established as a powerful tool to study cell-cell interactions in inflammatory EAE lesions in living animals. In EAE, central nervous system inflammation is strongly pronounced in the spinal cord, an organ in which 2P-IVM imaging is technically very challenging and has been limited to the lumbar spinal cord. Here, we describe a novel spinal cord window preparation allowing to use 2P-IVM to image immune cell interactions with the cervical spinal cord micro…
Lack of NG2 exacerbates neurological outcome and modulates glial responses after traumatic brain injury
2015
Traumatic brain injury (TBI) is a major cause of death and disability. The underlying pathophysiology is characterized by secondary processes including neuronal death and gliosis. To elucidate the role of the NG2 proteoglycan we investigated the response of NG2-knockout mice (NG2-KO) to TBI. Seven days after TBI behavioral analysis, brain damage volumetry and assessment of blood brain barrier integrity demonstrated an exacerbated response of NG2-KO compared to wild-type (WT) mice. Reactive astrocytes and expression of the reactive astrocyte and neurotoxicity marker Lcn2 (Lipocalin-2) were increased in the perilesional brain tissue of NG2-KO mice. In addition, microglia/macrophages with acti…
Progranulin protects against exaggerated axonal injury and astrogliosis following traumatic brain injury
2016
In response to traumatic brain injury (TBI) microglia/macrophages and astrocytes release inflammatory mediators with dual effects on secondary brain damage progression. The neurotrophic and anti-inflammatory glycoprotein progranulin (PGRN) attenuates neuronal damage and microglia/macrophage activation in brain injury but mechanisms are still elusive. Here, we studied histopathology, neurology and gene expression of inflammatory markers in PGRN-deficient mice (Grn-/- ) 24 h and 5 days after experimental TBI. Grn-/- mice displayed increased perilesional axonal injury even though the overall brain tissue loss and neurological consequences were similar to wild-type mice. Brain inflammation was …
Small endogenous molecules as moiety to improve targeting of CNS drugs.
2016
A major challenge in the development of novel neuro-therapeutic agents is to effectively overcome the blood-brain barrier (BBB), which acts as a 'working dynamic barrier'. The core problem in the treatment of neurodegenerative diseases is failed delivery of potential medicines due to their inadequate permeation rate. Areas covered: The present review gives a summary of endogenous moieties used in synthesizing prodrugs, derivatives and bioisosteric drugs appositely designed to structurally resemble physiological molecular entities able to be passively absorbed or carried by specific carrier proteins expressed at BBB level. In particular, this overview focuses on aminoacidic, glycosyl, purine…
Entropic Interactions between Two Knots on a Semiflexible Polymer.
2017
Two knots on a string can either be separated or intertwined, and may even pass through each other. At the microscopic scale, such transitions may occur spontaneously, driven by thermal fluctuations, and can be associated with a topological free energy barrier. In this manuscript, we study the respective location of a trefoil ( 3 1 ) and a figure-eight ( 4 1 ) knot on a semiflexible polymer, which is parameterized to model dsDNA in physiological conditions. Two cases are considered: first, end monomers are grafted to two confining walls of varying distance. Free energy profiles and transition barriers are then compared to a subset of free chains, which contain exactly one 3 1 and one 4 1 kn…
Protease‐activated receptor signaling in intestinal permeability regulation
2019
Protease-activated receptors (PARs) are a unique class of G-protein-coupled transmembrane receptors, which revolutionized the perception of proteases from degradative enzymes to context-specific signaling factors. Although PARs are traditionally known to affect several vascular responses, recent investigations have started to pinpoint the functional role of PAR signaling in the gastrointestinal (GI) tract. This organ is exposed to the highest number of proteases, either from the gut lumen or from the mucosa. Luminal proteases include the host's digestive enzymes and the proteases released by the commensal microbiota, while mucosal proteases entail extravascular clotting factors and the enzy…
A Simple Method to Predict Blood-Brain Barrier Permeability of Drug- Like Compounds Using Classification Trees
2017
Background: To know the ability of a compound to penetrate the blood-brain barrier (BBB) is a challenging task; despite the numerous efforts realized to predict/measure BBB passage, they still have several drawbacks. Methods: The prediction of the permeability through the BBB is carried out using classification trees. A large data set of 497 compounds (recently published) is selected to develop the tree model. Results: The best model shows an accuracy higher than 87.6% for training set; the model was also validated using 10-fold cross-validation procedure and through a test set achieving accuracy values of 86.1% and 87.9%, correspondingly. We give a brief explanation, in structural terms, o…
Molecular chaperones in the brain endothelial barrier: neurotoxicity or neuroprotection?
2019
Brain microvascular endothelial cells (BMECs) interact with astrocytes and pericytes to form the blood-brain barrier (BBB). Their compromised function alters the BBB integrity, which is associated with early events in the pathogenesis of cancer, neurodegenerative diseases, and epilepsy. Interestingly, these conditions also induce the expression of heat shock proteins (HSPs). Here we review the contribution of major HSP families to BMEC and BBB function. Although investigators mainly report protective effects of HSPs in brain, contrasted results were obtained in BMEC, which depend both on the HSP and on its location, intra- or extracellular. The therapeutic potential of HSPs must be scrupulo…
Th17 skewing in the GALT of a Crohn disease patient upon Lactobacillus rhamnosus GG consumption.
2015
We wish to report on a recent observation we made and that might represent a useful hint for the employment of the so called probiotics in the management of some pathological immune reactions of the gut. By analyzing GALT-associated T cells upon consumption of L. rhamnosus-GG, we obtained some hints that probiotics might have locoregional immunological effects mainly when administered in patients with IBDs rather than in individuals with non-inflamed gut mucosa.