scholarly journals Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain

2004 ◽  
Vol 183 (1) ◽  
pp. 235-241 ◽  
Author(s):  
C H J Verhoelst ◽  
V M Darras ◽  
S A Roelens ◽  
G M Artykbaeva ◽  
S Van der Geyten
Keyword(s):  
Epithelial Cells ◽  
Choroid Plexus ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Type I ◽  
Mrna Levels ◽  
Type Ii ◽  
Iodothyronine Deiodinase ◽  
Blood Brain ◽  
D2 Protein

It is widely accepted that type II iodothyronine deiodinase (D2) is mostly present in the brain, where it maintains the homeostasis of thyroid hormone (TH) levels. Although intensive studies have been performed on activity and mRNA levels of the deiodinases, very little is known about their expression at the protein level due to the lack of specific antisera. The current study reports the production of a specific D2 polyclonal antiserum and its use in the comparison of D2 protein distribution with that of type I (D1) and type III (D3) deiodinase protein in the choroid plexus at the blood–brain barrier level. Immunocytochemistry showed very high D2 protein expression in the choroid plexus, especially in the epithelial cells, whereas the D1 and D3 proteins were absent. Furthermore, dexamethasone treatment led to an up-regulation of the D2 protein in the choroid plexus. The expression of D2 protein in the choroid plexus led to a novel insight into the working mechanism of the uptake and transport of thyroid hormones along the blood–brain barrier in birds. It is hypothesized that D2 allows the prohormone thyroxine (T4) to be converted into the active 3,5,3′-triiodothyronine (T3). Within the choroidal epithelial cells. T3 is subsequently bound to its carrier protein, transthyretin (TTR), to allow transport through the cerebrospinal fluid. Neurons can thus not only be provided with a sufficient T3 level via the aid of the astrocytes, as was hypothesized previously based on in situ hybridization data, but also by means of T4 deiodination by D2, directly at the blood–brain barrier level.

The Blood-Brain Barrier Interface in Diabetes Mellitus: Dysfunctions, Mechanisms and Approaches to Treatment

2020 ◽  
Vol 26 (13) ◽  
pp. 1438-1447 ◽  
Author(s):  
William A. Banks
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Growth Factor ◽  
Matrix Metalloproteinases ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Type I ◽  
Type Ii ◽  
P Glycoprotein ◽  
Blood Brain

Diabetes mellitus (DM) is one of the most common diseases in the world. Among its effects are an increase in the risk of cognitive impairment, including Alzheimer’s disease, and blood-brain barrier (BBB) dysfunction. DM is characterized by high blood glucose levels that are caused by either lack of insulin (Type I) or resistance to the actions of insulin (Type II). The phenotypes of these two types are dramatically different, with Type I animals being thin, with low levels of leptin as well as insulin, whereas Type II animals are often obese with high levels of both leptin and insulin. The best characterized change in BBB dysfunction is that of disruption. The brain regions that are disrupted, however, vary between Type I vs Type II DM, suggesting that factors other than hyperglycemia, perhaps hormonal factors such as leptin and insulin, play a regionally diverse role in BBB vulnerability or protection. Some BBB transporters are also altered in DM, including P-glycoprotein, lowdensity lipoprotein receptor-related protein 1, and the insulin transporter as other functions of the BBB, such as brain endothelial cell (BEC) expression of matrix metalloproteinases (MMPs) and immune cell trafficking. Pericyte loss secondary to the increased oxidative stress of processing excess glucose through the Krebs cycle is one mechanism that has shown to result in BBB disruption. Vascular endothelial growth factor (VEGF) induced by advanced glycation endproducts can increase the production of matrix metalloproteinases, which in turn affects tight junction proteins, providing another mechanism for BBB disruption as well as effects on P-glycoprotein. Through the enhanced expression of the redox-related mitochondrial transporter ABCB10, redox-sensitive transcription factor NF-E2 related factor-2 (Nrf2) inhibits BEC-monocyte adhesion. Several potential therapies, in addition to those of restoring euglycemia, can prevent some aspects of BBB dysfunction. Carbonic anhydrase inhibition decreases glucose metabolism and so reduces oxidative stress, preserving pericytes and blocking or reversing BBB disruption. Statins or N-acetylcysteine can reverse the BBB opening in some models of DM, fibroblast growth factor-21 improves BBB permeability through an Nrf2-dependent pathway, and nifedipine or VEGF improves memory in DM models. In summary, DM alters various aspects of BBB function through a number of mechanisms. A variety of treatments based on those mechanisms, as well as restoration of euglycemia, may be able to restore BBB functions., including reversal of BBB disruption.

scholarly journals MRI phenotypes in MS

2019 ◽  
Vol 6 (2) ◽  
pp. e530 ◽  
Author(s):  
Christopher C. Hemond ◽  
Brian C. Healy ◽  
Shahamat Tauhid ◽  
Maria A. Mazzola ◽  
Francisco J. Quintana ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Lesion Volume ◽  
Type I ◽  
Type Ii ◽  
Hyperintense Lesion ◽  
Cross Sectional ◽  
Type Iv ◽  
Blood Brain ◽  
Conversion Rates

ObjectiveTo classify and immunologically characterize persons with MS based on brain lesions and atrophy and their associated microRNA profiles.MethodsCerebral T2-hyperintense lesion volume (T2LV) and brain parenchymal fraction (BPF) were quantified and used to define MRI phenotypes as follows: type I: low T2LV, low atrophy; type II: high T2LV, low atrophy; type III: low T2LV, high atrophy; type IV: high T2LV, high atrophy, in a large cross-sectional cohort (n = 1,088) and a subset with 5-year lngitudinal follow-up (n = 153). Serum miRNAs were assessed on a third MS cohort with 2-year MRI phenotype stability (n = 98).ResultsOne-third of the patients had lesion-atrophy dissociation (types II or III) in both the cross-sectional and longitudinal cohorts. At 5 years, all phenotypes had progressive atrophy (p < 0.001), disproportionally in type II (BPF −2.28%). Only type IV worsened in physical disability. Types I and II showed a 5-year MRI phenotype conversion rate of 33% and 46%, whereas III and IV had >90% stability. Type II switched primarily to IV (91%); type I switched primarily to II (47%) or III (37%). Baseline higher age (p = 0.006) and lower BPF (p < 0.001) predicted 5-year phenotype conversion. Each MRI phenotype demonstrated an miRNA signature whose underlying biology implicates blood-brain barrier pathology: hsa.miR.22.3p, hsa.miR.361.5p, and hsa.miR.345.5p were the most valid differentiators of MRI phenotypes.ConclusionsMRI-defined MS phenotypes show high conversion rates characterized by the continuation of either predominant neurodegeneration or inflammation and support the partial independence of these 2 measures. MicroRNA signatures of these phenotypes suggest a role for blood-brain barrier integrity.

scholarly journals Culture-Induced Changes in Blood—Brain Barrier Transcriptome: Implications for Amino-Acid Transporters in vivo

2009 ◽  
Vol 29 (9) ◽  
pp. 1491-1502 ◽  
Author(s):  
Ruth Lyck ◽  
Nadine Ruderisch ◽  
Anton G Moll ◽  
Oliver Steiner ◽  
Clemens D Cohen ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Amino Acid Transporters ◽  
Mrna Levels ◽  
Blood Brain ◽  
Barrier Formation ◽  
Platelet Endothelial Cell Adhesion ◽  
Induced Changes

Tight homeostatic control of brain amino acids (AA) depends on transport by solute carrier family proteins expressed by the blood—brain barrier (BBB) microvascular endothelial cells (BMEC). To characterize the mouse BMEC transcriptome and probe culture-induced changes, microarray analyses of platelet endothelial cell adhesion molecule-1-positive (PECAM1+) endothelial cells (ppMBMECs) were compared with primary MBMECs (pMBMEC) cultured in the presence or absence of glial cells and with b.End5 endothelioma cell line. Selected cell marker and AA transporter mRNA levels were further verified by reverse transcription real-time PCR. Regardless of glial coculture, expression of a large subset of genes was strongly altered by a brief culture step. This is consistent with the known dependence of BMECs on in vivo interactions to maintain physiologic functions, for example, tight barrier formation, and their consequent dedifferentiation in culture. Seven ( 4F2hc, Lat1, Taut, Snat3, Snat5, Xpct, and Cat1) of nine AA transporter mRNAs highly expressed in freshly isolated ppMBMECs were strongly downregulated for all cultures and two ( Snat2 and Eaat3) were variably regulated. In contrast, five AA transporter mRNAs with low expression in ppMBMECs, including y+ Lat2, xCT, and Snat1, were upregulated by culture. We hypothesized that the AA transporters highly expressed in ppMBMECs and downregulated in culture have a major in vivo function for BBB transendothelial transport.

scholarly journals Poly-ICLC preconditioning protects the blood-brain barrier against ischemic injuryin vitrothrough type I interferon signaling

2012 ◽  
Vol 123 ◽  
pp. 75-85 ◽  
Author(s):  
Raffaella Gesuete ◽  
Amy E. B. Packard ◽  
Keri B. Vartanian ◽  
Valerie K. Conrad ◽  
Susan L. Stevens ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Type I Interferon ◽  
Brain Barrier ◽  
Type I ◽  
Interferon Signaling ◽  
Blood Brain

The blood-brain barrier of the rat choroid plexus

1975 ◽  
Vol 181 (4) ◽  
pp. 779-789 ◽  
Author(s):  
Donald A. Davis ◽  
Thomas H. Milhorat
Keyword(s):  
Choroid Plexus ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

Blood-brain barrier-penetrating iduronate-2-sulfatase reduces brain glycosaminoglycans in mouse model of mucopolysaccharidosis type II

2018 ◽  
Vol 123 (2) ◽  
pp. S134
Author(s):  
Hiroyuki Sonoda ◽  
Hideto Morimoto ◽  
Eiji Yoden ◽  
Yuri Koshimura ◽  
Masafumi Kinoshita ◽  
...  
Keyword(s):  
Mouse Model ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Mucopolysaccharidosis Type ◽  
Type Ii ◽  
Mucopolysaccharidosis Type Ii ◽  
Blood Brain

scholarly journals Encephalitic Alphaviruses Exploit Caveola-Mediated Transcytosis at the Blood-Brain Barrier for Central Nervous System Entry

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hamid Salimi ◽  
Matthew D. Cain ◽  
Xiaoping Jiang ◽  
Robyn A. Roth ◽  
Wandy L. Beatty ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Viral Replication ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Type I ◽  
Brain Endothelial Cells ◽  
Blood Brain ◽  
Deficient Mice

ABSTRACT Venezuelan and western equine encephalitis viruses (VEEV and WEEV, respectively) invade the central nervous system (CNS) early during infection, via neuronal and hematogenous routes. While viral replication mediates host shutoff, including expression of type I interferons (IFN), few studies have addressed how alphaviruses gain access to the CNS during established infection or the mechanisms of viral crossing at the blood-brain barrier (BBB). Here, we show that hematogenous dissemination of VEEV and WEEV into the CNS occurs via caveolin-1 (Cav-1)-mediated transcytosis (Cav-MT) across an intact BBB, which is impeded by IFN and inhibitors of RhoA GTPase. Use of reporter and nonreplicative strains also demonstrates that IFN signaling mediates viral restriction within cells comprising the neurovascular unit (NVU), differentially rendering brain endothelial cells, pericytes, and astrocytes permissive to viral replication. Transmission and immunoelectron microscopy revealed early events in virus internalization and Cav-1 association within brain endothelial cells. Cav-1-deficient mice exhibit diminished CNS VEEV and WEEV titers during early infection, whereas viral burdens in peripheral tissues remained unchanged. Our findings show that alphaviruses exploit Cav-MT to enter the CNS and that IFN differentially restricts this process at the BBB. IMPORTANCE VEEV, WEEV, and eastern equine encephalitis virus (EEEV) are emerging infectious diseases in the Americas, and they have caused several major outbreaks in the human and horse population during the past few decades. Shortly after infection, these viruses can infect the CNS, resulting in severe long-term neurological deficits or death. Neuroinvasion has been associated with virus entry into the CNS directly from the bloodstream; however, the underlying molecular mechanisms have remained largely unknown. Here, we demonstrate that following peripheral infection alphavirus augments vesicular formation/trafficking at the BBB and utilizes Cav-MT to cross an intact BBB, a process regulated by activators of Rho GTPases within brain endothelium. In vivo examination of early viral entry in Cav-1-deficient mice revealed significantly lower viral burdens in the brain than in similarly infected wild-type animals. These studies identify a potentially targetable pathway to limit neuroinvasion by alphaviruses.

scholarly journals FGF21 Protects against Aggravated Blood-Brain Barrier Disruption after Ischemic Focal Stroke in Diabetic db/db Male Mice via Cerebrovascular PPARγ Activation

2020 ◽  
Vol 21 (3) ◽  
pp. 824 ◽  
Author(s):  
Yinghua Jiang ◽  
Li Lin ◽  
Ning Liu ◽  
Qingzhi Wang ◽  
Jing Yuan ◽  
...  
Keyword(s):  
Dna Binding ◽  
Blood Brain Barrier ◽  
Binding Activity ◽  
Brain Barrier ◽  
Fibroblast Growth Factor 21 ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Dna Binding Activity ◽  
Blood Brain ◽  
Junction Protein

Recombinant fibroblast growth factor 21 (rFGF21) has been shown to be potently beneficial for improving long-term neurological outcomes in type 2 diabetes mellitus (T2DM) stroke mice. Here, we tested the hypothesis that rFGF21 protects against poststroke blood–brain barrier (BBB) damage in T2DM mice via peroxisome proliferator-activated receptor gamma (PPARγ) activation in cerebral microvascular endothelium. We used the distal middle cerebral occlusion (dMCAO) model in T2DM mice as well as cultured human brain microvascular endothelial cells (HBMECs) subjected to hyperglycemic and inflammatory injury in the current study. We detected a significant reduction in PPARγ DNA-binding activity in the brain tissue and mRNA levels of BBB junctional proteins and PPARγ-targeting gene CD36 and FABP4 in cerebral microvasculature at 24 h after stroke. Ischemic stroke induced a massive BBB leakage two days after stroke in T2DM mice compared to in their lean controls. Importantly, all abnormal changes were significantly prevented by rFGF21 administration initiated at 6 h after stroke. Our in vitro experimental results also demonstrated that rFGF21 protects against hyperglycemia plus interleukin (IL)-1β-induced transendothelial permeability through upregulation of junction protein expression in an FGFR1 activation and PPARγ activity elevation-dependent manner. Our data suggested that rFGF21 has strong protective effects on acute BBB leakage after diabetic stroke, which is partially mediated by increasing PPARγ DNA-binding activity and mRNA expression of BBB junctional complex proteins. Together with our previous investigations, rFGF21 might be a promising candidate for treating diabetic stroke.

scholarly journals SILVER DEPOSITION IN THE CENTRAL NERVOUS SYSTEM AND THE HEMATOENCEPHALIC BARRIER STUDIED WITH THE ELECTRON MICROSCOPE

1955 ◽  
Vol 1 (2) ◽  
pp. 161-166 ◽  
Author(s):  
V. L. van Breemen ◽  
C. D. Clemente
Keyword(s):  
Choroid Plexus ◽  
Blood Brain Barrier ◽  
Cell Membranes ◽  
Area Postrema ◽  
Light And Electron Microscopy ◽  
Blood Stream ◽  
Brain Barrier ◽  
Perivascular Spaces ◽  
Silver Deposition ◽  
Blood Brain

For the purpose of studying the hematoencephalic barrier as it is concerned with silver circulating in the blood stream, silver nitrate was vitally administered to rats in their drinking water over periods of 6 to 8 months. The cerebrum, cerebellum, medulla, area postrema, and choroid plexus were prepared for light and electron microscopy. Silver deposition was found in the perivascular spaces in the choroid plexus, area postrema, in the medulla surrounding the area postrema, and in minute quantities in the cerebrum, cerebellum, and most of the medulla. Two levels of the hematoencephalic barrier were apparently demonstrated in our investigations. The endothelial linings of the vessels in the cerebrum, cerebellum, and medulla constitute the first threshold of the hematoencephalic barrier (specifically here, blood-brain barrier). The cell membranes adjacent to the perivascular spaces form the second threshold, as follows:—the neuroglial cell membranes in the cerebrum, cerebellum, and medulla (blood-brain barrier); the membranes of the neuroglial cells in the area postrema (blood-brain barrier); and the membranes of the epithelial cells of the choroid plexus (blood-cerebrospinal fluid barrier). This study deals with silver deposition and does not infer that the penetration of ionic silver, if present in the blood stream, would necessarily be limited to the regions described. Bleb-like structures were observed to cover the epithelial cell surfaces in the choroid plexus. They may be cellular projections increasing the cell surface area or they may be secretory droplets.

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