Op-brai150095 1598..1612
نویسندگان
چکیده
Blood–brain barrier function is driven by the influence of astrocyte-secreted factors. During neuroinflammatory responses the blood–brain barrier is compromised resulting in central nervous system damage and exacerbated pathology. Here, we identified endothelial netrin 1 induction as a vascular response to astrocyte-derived sonic hedgehog that promotes autocrine barrier properties during homeostasis and increases with inflammation. Netrin 1 supports blood–brain barrier integrity by upregulating endothelial junctional protein expression, while netrin 1 knockout mice display disorganized tight junction protein expression and barrier breakdown. Upon inflammatory conditions, blood–brain barrier endothelial cells significantly upregulated netrin 1 levels in vitro and in situ, which prevented junctional breach and endothelial cell activation. Finally, netrin 1 treatment during experimental autoimmune encephalomyelitis significantly reduced blood–brain barrier disruption and decreased clinical and pathological indices of disease severity. Our results demonstrate that netrin 1 is an important regulator of blood–brain barrier maintenance that protects the central nervous system against inflammatory conditions such as multiple sclerosis and experimental autoimmune encephalomyelitis.
منابع مشابه
Op-brai150095 1..15
Blood–brain barrier function is driven by the influence of astrocyte-secreted factors. During neuroinflammatory responses the blood–brain barrier is compromised resulting in central nervous system damage and exacerbated pathology. Here, we identified endothelial netrin 1 induction as a vascular response to astrocyte-derived sonic hedgehog that promotes autocrine barrier properties during homeos...
متن کاملMolecular dynamics: survey of methods for simulating the activity of proteins.
3.2. Energy Minimization 1592 3.3. Adiabatic Mapping 1593 3.4. Molecular Dynamics 1593 3.4.1. Simulated Environment 1595 3.4.2. SHAKE 1595 3.4.3. Experimental Conditions 1596 3.4.4. Solvation 1596 3.5. Langevin Dynamics 1597 3.6. Brownian Dynamics 1597 3.7. Monte Carlo 1598 3.8. Simulated Annealing 1598 3.9. Nondynamic Methods 1598 3.9.1. Conformational Sampling 1598 3.9.2. Principal Component ...
متن کاملNeutrophil gelatinase-associated lipocalin prior to cardiac surgery predicts acute kidney injury and mortality
OBJECTIVE We aimed to investigate whether preoperative serum neutrophil gelatinase-associated lipocalin (sNGALpre-op) predicted postoperative acute kidney injury (AKI) during hospitalisation and 1-year cardiovascular and all-cause mortality following adult cardiac surgery. METHODS This study was a post hoc analysis of the Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patie...
متن کاملObservations of Stellar Maser Sources with no IRAS Counterpart
We investigated stellar maser sources with no IRAS counterpart at the radio, middle-infrared, and nearinfrared wavelengths. A 43 GHz SiO maser search for 120 2MASS/MSX objects, and 10 OH 1612 MHz sources with no or a very faint MSX counterpart, resulted in 43 SiO detections: one OH 1612 MHz source, 2 near-infrared stars, and 40 MSX sources. Additional near-infrared J-, H-, and K-band observatio...
متن کامل