Role of Nitric Oxide on the Blood–Brain and Spinal Cord Barriers

2004 ◽  
pp. 191-229 ◽  
Author(s):  
HARI SHANKER SHARMA ◽  
PER ALM
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Blood Brain ◽  
Brain And Spinal Cord

scholarly journals Inactivation of Hedgehog signal transduction in adult astrocytes results in region-specific blood–brain barrier defects

2021 ◽  
Vol 118 (34) ◽  
pp. e2017779118
Author(s):  
Hui Wang ◽  
Zhiyan Xu ◽  
Ziyue Xia ◽  
Michael Rallo ◽  
Andrew Duffy ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Molecular Genetic ◽  
Blood Brain ◽  
Predominant Cell Type ◽  
Rostral Hypothalamus ◽  
Hh Signaling ◽  
Paracellular Diffusion ◽  
Hedgehog Signal ◽  
Mouse Central Nervous System

In this study, we use molecular genetic approaches to clarify the role of the Hedgehog (Hh) pathway in regulating the blood–brain/spinal cord barrier (BBB) in the adult mouse central nervous system (CNS). Our work confirms and extends prior studies to demonstrate that astrocytes are the predominant cell type in the adult CNS that transduce Hh signaling, revealed by the expression of Gli1, a target gene of the canonical pathway that is activated in cells receiving Hh, and other key pathway transduction components. Gli1+ (Hh-responsive) astrocytes are distributed in specific regions of the CNS parenchyma, including layers 4/5/6 of the neocortex, hypothalamus, thalamus, and spinal cord, among others. Notably, although BBB properties in endothelial cells are normally regulated by both paracellular and transcellular mechanisms, conditional inactivation of Hh signaling in astrocytes results in transient, region-specific BBB defects that affect transcytosis but not paracellular diffusion. These findings stand in contrast to prior studies that implicated astrocytes as a source of Sonic hedgehog that limited extravasation via both mechanisms [J. I. Alvarez et al., Science 334, 1727–1731 (2011)]. Furthermore, using three distinct Cre driver lines as well as pharmacological approaches to inactivate Hh-pathway transduction globally in CNS astrocytes, we find that these specific BBB defects are only detected in the rostral hypothalamus and spinal cord but not the cortex or other regions where Gli1+ astrocytes are found. Together, our data show that Gli1+ Hh-responsive astrocytes have regionally distinct molecular and functional properties and that the pathway is required to maintain BBB properties in specific regions of the adult mammalian CNS.

Opioid and alcohol action: The role of brain and spinal cord innate immune signalling

2010 ◽  
Vol 24 ◽  
pp. S19
Author(s):  
M.R. Hutchinson ◽  
Y. Wu ◽  
L. Liu ◽  
S. Phipps ◽  
K.C. Rice ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Innate Immune ◽  
Brain And Spinal Cord

scholarly journals Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids, with Cranial and Caudal Extension

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Mahmood Mubasher ◽  
Aseel Sukik ◽  
Ahmed Hassan El Beltagi ◽  
Ali Rahil
Keyword(s):  
Spinal Cord ◽  
Lower Limbs ◽  
High Dose ◽  
Oral Corticosteroids ◽  
Dose Oral ◽  
Multiple Levels ◽  
Romberg Test ◽  
Brain And Spinal Cord ◽  
The Brain

A 23-year-old lady presented with vertigo and imbalance in walking, blurring of vision, diplopia, and headache, in addition to numbness in the lower limbs over a period of six days. On examination patient had nystagmus, ataxia, positive Romberg test, and hyperreflexia. MRI examination of the brain and spinal cord showed evidence of faint bright signal intensity foci in T2/FLAIR involving bilateral cerebral hemispheres, subcortical deep white matter, bilateral thalami, posterior pons and left brachium pontis, and basal ganglia, with small nodular enhancement that aligned along curvilinear structures; those lesions also were apparent along the spinal cord at multiple levels. The clinical and radiological features suggested CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) syndrome. Symptoms improved dramatically with high dose oral corticosteroids. Our report addresses the radiological and clinical pattern of a case of CLIPPERS rhombencephalitis, with added superior and inferior extension to involve the brain and spinal cord, which is to emphasize the importance of raising the awareness of this disease and the combined role of radiologist and physicians for the diagnosis of this potentially treatable entity, responsive to glucocorticosteroid immunosuppression.

61 UNVEILING THE ROLE OF LIPIDS IN ORGANOGESIS: MOLECULAR ANATOMY BY DESORPTION ELECTROSPRAY IONIZATION MASS SPECTROMETRY IMAGING MASS SPECTROMETRY

2016 ◽  
Vol 28 (2) ◽  
pp. 160
Author(s):  
V. Pirro ◽  
P. O. Favaron ◽  
C. R. Ferreira ◽  
L. S. Eberlin ◽  
R. S. Barreto ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Spinal Cord ◽  
Desorption Electrospray Ionization ◽  
Ionization Mass ◽  
Differential Distribution ◽  
Desi Ms ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Digestive Glands

Even though the role of lipids in pandemic diseases such as obesity and diabetes is a focus of increasing research, the role of lipids during organogenesis, when diverse diseases may be triggered, is unexplored. Also, pig embryonic tissues represent an attractive option for organ transplantation. This study introduces a detailed morphological analysis of swine fetal tissues with matching location of lipids acquired by desorption electrospray ionization mass spectrometry (DESI-MS) imaging for the study of differential distribution of free fatty acids (FFA) and phospholipids (PL) in specific organs during fetal development. Samples from a pig fetuses around Day 50 of pregnancy were sectioned at a cryotome and mounted onto glass slides. Fixative agents were not used. DESI-MS images were run with a step size of 300 µm using a morphologically friendly (non-destructive) solvent combination, namely dimethylformamide/acetonitrile 1 : 1 (v/v). Data were acquired in the negative ion mode in the m/z range of 150 to 1000 from different sections representing the whole swine fetus body. Ion images were constructed using BioMAP software. After imaging, the whole-body tissue samples were stained with hematoxylin and eosin (H&E) and were overlaid to the DESI-MS lipid images. Differential distribution of FFA, phosphatidylcholines (PC), phosphatidylserines (PS), sulphatides (ST), and phosphatidylinositols (PI) was observed among organs, especially on nervous and circulatory systems, and digestive glands. Most lipids concentrated in the brain, spinal cord, and digestive glands such as the liver. For example, arachidonic acid was most abundant in neuronal tissue, whereas docosahexaenoic acid predominated in the liver and digestive glands. Distribution of PS (36 : 1) of m/z 788 was observed in all tissues except for the digestive system, but PS (40 : 6) of m/z 834.7 was exclusive of brain and spinal cord. Lipids related to brain and spinal cord were mostly polyunsaturated fatty acids as well as specific PS lipids. Arachidonic and eicosatrienoic acids are more concentrated in hindbrain and spinal cord, whereas PS was more abundant in the brain than in the spinal cord. There is no information on PS chemical composition during brain and spinal cord development, but PS concentration in the nervous tissue membranes varies with age, brain areas, cell type, and subcellular components. Several reports indicate that alteration in PS synthesis might participate in the mechanism of brain damage. Also, PS has been found to be altered in brain tumours. Oleic acid, fatty acid dimers, and the signalling lipid PI (38 : 3) were most significant for the digestive system and liver. Liver is one of the main organs involved in fatty acid metabolism (besides adipose tissue and muscle). By overlying morphological and molecular information, lipids seem to be a major player in the organogenesis process.

scholarly journals Mrp1 is Essential for Sphingolipid Signaling to P-Glycoprotein in Mouse Blood–Brain and Blood–Spinal Cord Barriers

2012 ◽  
Vol 33 (3) ◽  
pp. 381-388 ◽  
Author(s):  
Tara A Cartwright ◽  
Christopher R Campos ◽  
Ronald E Cannon ◽  
David S Miller
Keyword(s):  
Spinal Cord ◽  
Endothelial Cells ◽  
Transport Activity ◽  
Wild Type ◽  
Mouse Blood ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Tnf Α ◽  
Glycoprotein Transport ◽  
Brain And Spinal Cord

At the blood–brain and blood–spinal cord barriers, P-glycoprotein, an ATP-driven drug efflux pump, is a major obstacle to central nervous system (CNS) pharmacotherapy. Recently, we showed that signaling through tumor necrosis factor-α (TNF-α), sphingolipids, and sphingosine-1-phosphate receptor 1 (S1PR1) rapidly and reversibly reduced basal P-glycoprotein transport activity in the rat blood–brain barrier. The present study extends those findings to the mouse blood–brain and blood–spinal cord barriers and, importantly, identifies multidrug resistance-associated protein 1 (Mrp1, Abcc1) as the transporter that mediates S1P efflux from brain and spinal cord endothelial cells. In brain and spinal cord capillaries isolated from wild-type mice, TNF-α, sphingosine, S1P, the S1PR agonist fingolimod (FTY720), and its active, phosphorylated metabolite, FTY720P, reduced P-glycoprotein transport activity; these effects were abolished by a specific S1PR1 antagonist. In brain and spinal cord capillaries isolated from Mrp1-null mice, neither TNF-α nor sphingosine nor FTY720 reduced P-glycoprotein transport activity. However, S1P and FTY720P had the same S1PR1-dependent effects on transport activity as in capillaries from wild-type mice. Thus, deletion of Mrp1 alone terminated endogenous signaling to S1PR1. These results identify Mrp1 as the transporter essential for S1P efflux from the endothelial cells and thus for inside-out S1P signaling to P-glycoprotein at the blood–brain and blood–spinal cord barriers.

scholarly journals Age-Dependent Poliovirus Replication in the Mouse Central Nervous System Is Determined by Internal Ribosome Entry Site-Mediated Translation

2006 ◽  
Vol 80 (6) ◽  
pp. 2589-2595 ◽  
Author(s):  
Steven Kauder ◽  
Sherry Kan ◽  
Vincent R. Racaniello
Keyword(s):  
Spinal Cord ◽  
Internal Ribosome Entry Site ◽  
Species Specificity ◽  
Entry Site ◽  
Internal Ribosome Entry ◽  
Adult Mice ◽  
Poliovirus Receptor ◽  
Mouse Cells ◽  
Brain And Spinal Cord

ABSTRACT Mouse cells are not permissive for the replication of human rhinovirus type 2 (HRV2). To determine the role of the HRV2 internal ribosome entry site (IRES) in determining species specificity, a recombinant poliovirus (P1/HRV2) was constructed by substituting the poliovirus IRES with the IRES from HRV2. This recombinant virus replicated in all human and murine cell lines examined, demonstrating that the HRV2 IRES does not limit viral replication in transformed murine cells. P1/HRV2 replicated in the brain and spinal cord in neonatal but not adult mice transgenic for the poliovirus receptor, CD155. Passage of P1/HRV2 in mice led to selection of a virus that caused paralysis in neonatal mice. To determine the relationship between HRV2 IRES-mediated translation and replication of P1/HRV2 in mice, recombinant human adenoviruses were used to express bicistronic mRNAs in murine organs. The results demonstrate that the HRV2 IRES mediates translation in organs of neonatal but not adult mice. These findings show that HRV2 IRES-mediated translation is a determinant of virus replication in the murine brain and spinal cord and suggest that the IRES determines the species specificity of HRV2 infection.

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