scholarly journals Transport of CRH from mouse brain directly affects peripheral production of β-endorphin by the spleen

1997 ◽  
Vol 273 (6) ◽  
pp. E1083-E1089 ◽  
Author(s):  
J. Martin Martins ◽  
William A. Banks ◽  
Abba J. Kastin
Keyword(s):  
Pituitary Gland ◽  
Blood Brain Barrier ◽  
Mouse Brain ◽  
Brain Barrier ◽  
Regulatory Function ◽  
Corticotropin Releasing Hormone ◽  
Peripheral Organ ◽  
Releasing Hormone ◽  
Peripheral Production ◽  
The Brain

The blood-brain barrier (BBB) regulates the passage of substances between the brain and the periphery. It has not been shown that the secretion from the brain of a small amount of a substance can directly affect the periphery by transport across the BBB. We found that central injection of radioactively labeled corticotropin-releasing hormone (CRH) resulted in the accumulation of intact CRH in the spleen. CRH also increased splenic β-endorphin, an effect not blocked by pretreatment with dexamethasone. Inhibition of the secretion of CRH from the brain by colchicine resulted in decreased accumulation of CRH in the spleen and also decreased splenic β-endorphin. Similar findings occurred in the pituitary gland. The results show that the passage of labeled CRH from the brain can directly affect a peripheral organ, thus emphasizing the regulatory function of the BBB.

scholarly journals The Blood–Brain Barrier Creatine Transporter is a Major Pathway for Supplying Creatine to the Brain

2002 ◽  
Vol 22 (11) ◽  
pp. 1327-1335 ◽  
Author(s):  
Sumio Ohtsuki ◽  
Masanori Tachikawa ◽  
Hitomi Takanaga ◽  
Hidemi Shimizu ◽  
Masahiko Watanabe ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Mouse Brain ◽  
Brain Barrier ◽  
Major Pathway ◽  
Creatine Transporter ◽  
Blood Brain ◽  
Creatine Uptake ◽  
Capillary Endothelial Cells ◽  
The Brain

Although creatine plays a pivotal role in the storage of phosphate-bound energy in the brain, the source of cerebral creatine is still unclear. The authors examined the contribution made by the creatine transporter (CRT) at the blood–brain barrier in supplying creatine to the brain from blood. An in vivo intravenous administration study suggested that creatine is continuously transported from the blood to the brain against the creatine concentration gradient that exists between brain and blood. Conditionally immortalized mouse brain capillary endothelial cells (TM-BBB) exhibited creatine uptake, which is Na+ and Cl− dependent and inhibited by CRT inhibitors, such as β-guanidinopropionate and guanidinoacetate. Northern blot and immunoblot analyses demonstrated that CRT is expressed in TM-BBB cells and isolated mouse brain microvessels. Moreover, high expression of CRT was observed in the mouse brain capillaries by confocal immunofluorescent microscopy. These results suggest that CRT plays an important role in supplying creatine to the brain via the blood–brain barrier.

scholarly journals A Novel Method to Stimulate Lymphatic Clearance of Beta-Amyloid from Mouse Brain Using Non-invasive Music-Induced Opening of the Blood-Brain Barrier with EEG Markers

2021 ◽  
Author(s):  
Oxana Semyachkina-Glushkovskaya ◽  
Alexander Khorovodov ◽  
Ivan Fedosov ◽  
Alexey Pavlov ◽  
Alexander Shirokov ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Mouse Brain ◽  
Protein A ◽  
Magnetic Resonance Tomography ◽  
Confocal Imaging ◽  
Brain Barrier ◽  
Fluctuation Analysis ◽  
Non Invasive ◽  
Blood Brain ◽  
The Brain

The lymphatic system of the brain meninges and head plays a crucial role in the clearance of amyloid-β protein (Aβ), a peptide thought to be pathogenic in Alzheimer’s disease (AD), from the brain. The development of methods to modulate lymphatic clearance of Aβ from the brain coild be a revolutionary step in the therapy of AD. The opening of the blood-brain barrier (OBBB) by focused ultrasound is considered as a possible tool for stimulation of clearance of Aβ from the brain of humans and animals. Here, we propose an alternative method of non-invasive music-induced OBBB that is accompanied by the activation of clearance of fluorescent Aβ (Fαβ) from the mouse brain. Using confocal imaging, fluorescence microscopy and magnetic resonance tomography, we clearly demonstrate that OBBB by music stimulates the movement of Fαβ and Omniscan in the cerebrospinal fluid and lymphatic clearance of Fαβ from the brain. We propose the extended detrended fluctuation analysis (EDFA) as a promising method for the identification of OBBB markers in the electroencephalographic (EEG) patterns. These pilot results suggest that music-induced OBBB and the EDFA analysis of EEG can be a non-invasive, low cost, labelling free, clinical perspective and completely new approach for the treatment and monitoring of AD.

scholarly journals Curcumin Oligosaccharides (Gluco-oligosaccharides) Penetrate the Blood-Brain Barrier in Mouse Brain: Glycoside (Polysaccharide) Modification Approach for Brain Drug Delivery Across the Blood-Brain Barrier and Tumor Drug Delivery

2020 ◽  
Vol 15 (11) ◽  
pp. 1934578X2095365
Author(s):  
Hiroki Hamada ◽  
Takahiro Nakayama ◽  
Kei Shimoda ◽  
Nobuyasu Matsuura ◽  
Hatsuyuki Hamada ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Mouse Brain ◽  
Brain Barrier ◽  
C57bl Mouse ◽  
Large Tumor ◽  
Brain Drug Delivery ◽  
Blood Brain ◽  
Delivery Technique ◽  
The Brain

In order to expand our drug delivery technique by glycosylation of chemical into brain delivery, it was demonstrated that oligosaccharide and monosaccharide modifications of curcumin enhanced its crossing ability of the blood-brain barrier (BBB) in mice. The brain sample prepared by glycosidase-catalyzed hydrolysis of brain tissue homogenates of mice, to which curcumin gluco-oligosaccharides were intraperitoneally injected, contained curcumin at 116 ng/1 g of tissue of brain, indicating that curcumin modified with gluco-oligosaccharides residues can smoothly cross the BBB in mouse brain. The brain samples of mice, which were treated with curcumin monosaccharide or curcumin itself, contained curcumin at 18 ng and 0 ng per 1 g of tissue of brain, respectively. On the other hand, after the administration of curcumin gluco-oligosaccharides to C57BL mouse with a large tumor for 5 days, the tumor disappeared.

scholarly journals Imaging Brain Amyloid of Alzheimer Disease in Vivo in Transgenic Mice with an Aβ Peptide Radiopharmaceutical

2002 ◽  
Vol 22 (2) ◽  
pp. 223-231 ◽  
Author(s):  
Hwa Jeong Lee ◽  
Yun Zhang ◽  
Chunni Zhu ◽  
Karen Duff ◽  
William M. Pardridge
Keyword(s):  
Alzheimer Disease ◽  
Transgenic Mice ◽  
Transgenic Mouse ◽  
Blood Brain Barrier ◽  
Mouse Brain ◽  
Brain Barrier ◽  
Blood Brain ◽  
Aβ Amyloid ◽  
The Brain

Aβ1–40 is a potential peptide radiopharmaceutical that could be used to image the brain Aβ amyloid of Alzheimer disease in vivo, should this peptide be made transportable through the blood–brain barrier in vivo. The blood–brain barrier transport of [125I]-Aβ1–40 in a transgenic mouse model was enabled by conjugation to the rat 8D3 monoclonal antibody to the mouse transferrin receptor. The Aβ1–40–8D3 conjugate is a bifunctional molecule that binds the blood–brain barrier TfR and undergoes transport into brain and binds the Aβ amyloid plaques of Alzheimer disease. App SW/ Psen1 double-transgenic and littermate control mice were administered either unconjugated Aβ1–40 or the Aβ1–40–8D3 conjugate intravenously, and brain scans were obtained 6 hours later. Immunocytochemical analysis showed abundant Aβ immunoreactive plaques in the brains of the App SW/ Psen1 transgenic mice and there was a selective retention of radioactivity in the brains of these mice at 6 hours after intravenous administration of the conjugate. In contrast, there was no selective sequestration either of the conjugate in control littermate mouse brain or of unconjugated Aβ1–40 in transgenic mouse brain. In conclusion, the results show that it is possible to image the Aβ amyloid burden in the brain in vivo with an amyloid imaging agent, provided the molecule is conjugated to a blood–brain barrier drug-targeting system.

scholarly journals Corticotropin-Releasing Hormone Receptor-1 in Cerebral Microvessels Changes during Development and Influences Urocortin Transport across the Blood-Brain Barrier

Endocrinology ◽  
2009 ◽  
Vol 151 (3) ◽  
pp. 1221-1227 ◽  
Author(s):  
Hung Hsuchou ◽  
Abba J. Kastin ◽  
Xiaojun Wu ◽  
Hong Tu ◽  
Weihong Pan
Keyword(s):  
Blood Brain Barrier ◽  
Hormone Receptor ◽  
Brain Barrier ◽  
Receptor Subtypes ◽  
Multiple Time ◽  
Corticotropin Releasing Hormone ◽  
Cerebral Microvessels ◽  
Releasing Hormone ◽  
Adult Mice ◽  
Blood Brain

In this study we tested the hypothesis that receptor-mediated transport of urocortin across the blood-brain barrier (BBB) undergoes developmental changes. Urocortin is a peptide produced by both selective brain regions and peripheral organs, and it is involved in feeding, memory, mood, cardiovascular functions, and immune regulation. In BBB studies with multiple-time regression analysis, we found that neonatal mice had a significant influx of 125I-urocortin. By contrast, adult mice did not transport urocortin across the BBB. Quantitative RT-PCR showed that corticotropin-releasing hormone receptor (CRHR)-1 was developmentally regulated in enriched cerebral microvessels as well as hypothalamus, being significantly higher in neonatal than adult mice. This change was less dramatic in agouti viable yellow mice, a strain that develops adult-onset obesity. The level of expression of CRHR1 mRNA was 33-fold higher in the microvessels than in hypothalamic homogenates. The mRNA for CRHR2 was less abundant in both regions and less prone to changes with development or the agouti viable yellow mutation. Supported by previous findings of receptor-mediated endocytosis of urocortin, these results suggest that permeation of urocortin across the BBB is dependent on the level of CRHR1 expression in cerebral microvessels. These novel findings of differential regulation of CRH receptor subtypes help elucidate developmental processes in the brain, particularly for the urocortin system.

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

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