scholarly journals Celecoxib Alleviates Radiation-Induced Brain Injury in Rats by Maintaining the Integrity of Blood-Brain Barrier

Dose-Response ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 155932582110243
Author(s):  
Xiaoting Xu ◽  
Hao Huang ◽  
Yu Tu ◽  
Jiaxing Sun ◽  
Yaozu Xiong ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Brain Injury ◽  
Protective Effect ◽  
Blood Brain Barrier ◽  
Vascular Endothelial Cells ◽  
Brain Barrier ◽  
Vascular Endothelial ◽  
Blood Brain ◽  
Radiation Induced ◽  
Cox 2

The underlying mechanisms of radiation-induced brain injury are poorly understood, although COX-2 inhibitors have been shown to reduce brain injury after irradiation. In the present study, the effect of celecoxib (a selective COX-2 inhibitor) pretreatment on radiation-induced injury to rat brain was studied by means of histopathological staining, evaluation of integrity of blood-brain barrier and detection of the expressions of inflammation-associated genes. The protective effect of celecoxib on human brain microvascular endothelial cells (HBMECs) against irradiation was examined and the potential mechanisms were explored. Colony formation assay and apoptosis assay were undertaken to evaluate the effect of celecoxib on the radiosensitivity of the HBMECs. ELISA was used to measure 6-keto-prostaglandin F1α (6-keto-PGF1α) and thromboxane B2 (TXB2) secretion. Western blot was employed to examine apoptosis-related proteins expressions. It was found that celecoxib protected rat from radiation-induced brain injury by maintaining the integrity of the blood-brain barrier and reducing inflammation in rat brain tissues. In addition, celecoxib showed a significant protective effect on HBMECs against irradiation, which involves inhibited apoptosis and decreased TXB2/6-keto-PGF1α ratio in brain vascular endothelial cells. In conclusion, celecoxib could alleviate radiation-induced brain injury in rats, which may be partially due to the protective effect on brain vascular endothelial cells from radiation-induced apoptosis.

scholarly journals Reduced Levels of A20 Protein Prompted RIPK1-Dependent Apoptosis of Vascular Endothelial Cells and Blood–Brain Barrier Breakdown in CIRI

2021 ◽  
Author(s):  
Ying Li ◽  
Chaonan Yang ◽  
Yuting Yang ◽  
Huijie Li ◽  
Xiaohui Wu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Ischemia Reperfusion Injury ◽  
Vascular Endothelial Cells ◽  
Ischemia Reperfusion ◽  
Brain Barrier ◽  
Vascular Endothelial ◽  
Ischemic Reperfusion ◽  
Blood Brain ◽  
Cerebral Ischemia Reperfusion Injury

Abstract Blood–brain barrier (BBB) leakage is an important cause of the exacerbation of pathological features of ischemia and reperfusion. However, the specific mechanism of cell death of vascular endothelial cells is not clear. It was found that ischemic reperfusion resulted in RIPK1 activation in vascular endothelial cells and induced cells to undergo subsequent RIPK1-dependent apoptosis (RDA). Inhibition of RIPK1 significantly reduced BBB breakdown and brain damage. The aim of this study is to investigate the mechanism of RIPK1 in the BBB leakage during the ischemia reperfusion procedure.In this study, the role of RIPK1 in the development of cerebral ischemia reperfusion injury (CIRI) was investigated by immunohistochemical approaches on KO or mutant mice. It was discovered by proteomics that autophagy activation resulting from ischemia and reperfusion significantly downregulated the level of A20 protein in vascular endothelial cells. A20 is an important protein that regulates RIPK1 and RDA. It was hypothesized that activation of autophagy in vascular endothelial cells caused by ischemic reperfusion led to a decrease in A20 protein, which, in turn, caused the activation of RIPK1 and the occurrence of RDA, leading to leakage of the blood–brain barrier. The findings in this study revealed the role of RIPK1 in vascular endothelial cell death and BBB leakage upon cerebral ischemia reperfusion injury (CIRI), and these findings provide a novel perspective for the treatment of ischemic reperfusion.

scholarly journals The Structure and Function of the Glycocalyx and Its Connection With Blood-Brain Barrier

2021 ◽  
Vol 15 ◽  
Author(s):  
Jing Jin ◽  
Fuquan Fang ◽  
Wei Gao ◽  
Hanjian Chen ◽  
Jiali Wen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Cell Activation ◽  
Vascular Endothelial Cells ◽  
Neurological Diseases ◽  
Basement Membranes ◽  
Brain Barrier ◽  
Endothelial Glycocalyx ◽  
Vascular Endothelial ◽  
Blood Brain

The vascular endothelial glycocalyx is a dense, bush-like structure that is synthesized and secreted by endothelial cells and evenly distributed on the surface of vascular endothelial cells. The blood-brain barrier (BBB) is mainly composed of pericytes endothelial cells, glycocalyx, basement membranes, and astrocytes. The glycocalyx in the BBB plays an indispensable role in many important physiological functions, including vascular permeability, inflammation, blood coagulation, and the synthesis of nitric oxide. Damage to the fragile glycocalyx can lead to increased permeability of the BBB, tissue edema, glial cell activation, up-regulation of inflammatory chemokines expression, and ultimately brain tissue damage, leading to increased mortality. This article reviews the important role that glycocalyx plays in the physiological function of the BBB. The review may provide some basis for the research direction of neurological diseases and a theoretical basis for the diagnosis and treatment of neurological diseases.

scholarly journals Podocalyxin is required for maintaining blood–brain barrier function during acute inflammation

2019 ◽  
Vol 116 (10) ◽  
pp. 4518-4527 ◽  
Author(s):  
Jessica Cait ◽  
Michael R. Hughes ◽  
Matthew R. Zeglinski ◽  
Allen W. Chan ◽  
Sabrina Osterhof ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Barrier Function ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Focal Adhesions ◽  
Brain Barrier ◽  
Cortical Actin ◽  
Inflammatory Conditions ◽  
Blood Brain

Podocalyxin (Podxl) is broadly expressed on the luminal face of most blood vessels in adult vertebrates, yet its function on these cells is poorly defined. In the present study, we identified specific functions for Podxl in maintaining endothelial barrier function. Using electrical cell substrate impedance sensing and live imaging, we found that, in the absence of Podxl, human umbilical vein endothelial cells fail to form an efficient barrier when plated on several extracellular matrix substrates. In addition, these monolayers lack adherens junctions and focal adhesions and display a disorganized cortical actin cytoskeleton. Thus, Podxl has a key role in promoting the appropriate endothelial morphogenesis required to form functional barriers. This conclusion is further supported by analyses of mutant mice in which we conditionally deleted a floxed allele ofPodxlin vascular endothelial cells (vECs) using Tie2Cre mice (PodxlΔTie2Cre). Although we did not detect substantially altered permeability in naïve mice, systemic priming with lipopolysaccharide (LPS) selectively disrupted the blood–brain barrier (BBB) inPodxlΔTie2Cremice. To study the potential consequence of this BBB breach, we used a selective agonist (TFLLR-NH2) of the protease-activated receptor-1 (PAR-1), a thrombin receptor expressed by vECs, neuronal cells, and glial cells. In response to systemic administration of TFLLR-NH2, LPS-primedPodxlΔTie2Cremice become completely immobilized for a 5-min period, coinciding with severely dampened neuroelectric activity. We conclude that Podxl expression by CNS tissue vECs is essential for BBB maintenance under inflammatory conditions.

scholarly journals Effect of AFM Nanoindentation Loading Rate on the Characterization of Mechanical Properties of Vascular Endothelial Cell

Micromachines ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 562
Author(s):  
Lei Wang ◽  
Liguo Tian ◽  
Wenxiao Zhang ◽  
Zuobin Wang ◽  
Xianping Liu
Keyword(s):  
Mechanical Properties ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Loading Rate ◽  
Vascular Endothelial Cells ◽  
Brain Barrier ◽  
Vascular Endothelial ◽  
Mechanical Responses

Vascular endothelial cells form a barrier that blocks the delivery of drugs entering into brain tissue for central nervous system disease treatment. The mechanical responses of vascular endothelial cells play a key role in the progress of drugs passing through the blood–brain barrier. Although nanoindentation experiment by using AFM (Atomic Force Microscopy) has been widely used to investigate the mechanical properties of cells, the particular mechanism that determines the mechanical response of vascular endothelial cells is still poorly understood. In order to overcome this limitation, nanoindentation experiments were performed at different loading rates during the ramp stage to investigate the loading rate effect on the characterization of the mechanical properties of bEnd.3 cells (mouse brain endothelial cell line). Inverse finite element analysis was implemented to determine the mechanical properties of bEnd.3 cells. The loading rate effect appears to be more significant in short-term peak force than that in long-term force. A higher loading rate results in a larger value of elastic modulus of bEnd.3 cells, while some mechanical parameters show ambiguous regulation to the variation of indentation rate. This study provides new insights into the mechanical responses of vascular endothelial cells, which is important for a deeper understanding of the cell mechanobiological mechanism in the blood–brain barrier.

scholarly journals Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood–brain barrier and blood–retina barrier development and maintenance

2018 ◽  
Vol 115 (50) ◽  
pp. E11827-E11836 ◽  
Author(s):  
Yanshu Wang ◽  
Chris Cho ◽  
John Williams ◽  
Philip M. Smallwood ◽  
Chi Zhang ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Vascular Endothelial Cells ◽  
Brain Barrier ◽  
Small Contribution ◽  
Vascular Endothelial ◽  
Loss Of Function ◽  
Regional Heterogeneity ◽  
Signaling Systems ◽  
Blood Brain ◽  
Partial Redundancy

β-Catenin signaling controls the development and maintenance of the blood–brain barrier (BBB) and the blood–retina barrier (BRB), but the division of labor and degree of redundancy between the two principal ligand–receptor systems—the Norrin and Wnt7a/Wnt7b systems—are incompletely defined. Here, we present a loss-of-function genetic analysis of postnatal BBB and BRB maintenance in mice that shows striking threshold and partial redundancy effects. In particular, the combined loss of Wnt7a and Norrin or Wnt7a and Frizzled4 (Fz4) leads to anatomically localized BBB defects that are far more severe than observed with loss of Wnt7a, Norrin, or Fz4 alone. In the cerebellum, selective loss of Wnt7a in glia combined with ubiquitous loss of Norrin recapitulates the phenotype observed with ubiquitous loss of both Wnt7a and Norrin, implying that glia are the source of Wnt7a in the cerebellum. Tspan12, a coactivator of Norrin signaling in the retina, is also active in BBB maintenance but is less potent than Norrin, consistent with a model in which Tspan12 enhances the amplitude of the Norrin signal in vascular endothelial cells. Finally, in the context of a partially impaired Norrin system, the retina reveals a small contribution to BRB development from the Wnt7a/Wnt7b system. Taken together, these experiments define the extent of CNS region-specific cooperation for several components of the Norrin and Wnt7a/Wnt7b systems, and they reveal substantial regional heterogeneity in the extent to which partially redundant ligands, receptors, and coactivators maintain the BBB and BRB.

Sign in / Sign up

Export Citation Format

Share Document