scholarly journals Cerebral Blood Flow and Blood—Brain Influx of Some Neutral Amino Acids in Control and Hypothyroid 16-Day-Old Rats

1985 ◽  
Vol 5 (2) ◽  
pp. 318-326 ◽  
Author(s):  
J. M. Lefauconnier ◽  
P. Lacombe ◽  
G. Bernard
Keyword(s):  
Amino Acids ◽  
Plasma Volume ◽  
Brain Capillary ◽  
Neutral Amino Acids ◽  
Luminal Membrane ◽  
Brain Extraction ◽  
Blood Brain ◽  
Capillary Endothelial Cells ◽  
Capillary Bed ◽  
The Brain

Rats were made hypothyroid by a daily subcutaneous injection of propylthiouracil beginning the first day after birth. CBF, brain plasma volume, blood–brain extraction, and influx of some neutral amino acids were studied in 16-day-old animals. In hypothyroid rats, the brain plasma volume was decreased by ∼30%. CBF was decreased by >50%. This decrease was the highest in cerebellum. Blood–brain extraction of small neutral amino acids (alanine, serine, cysteine) was greatly enhanced. This greater extraction compensated for the decreased supply of alanine brought about by its decreased plasma concentration and the lower CBF. In contrast, the extraction of the large amino acids tested (leucine, phenylalanine) was hardly increased, and the influx of phenylalanine was slightly decreased. These results suggest an alteration in the maturation of the brain capillary bed and capillary transport for neutral amino acids in hypothyroidism. The differential effect of hypothyroidism on some small and large amino acids is an additional argument for the existence of two systems of transport for neutral amino acids at the luminal membrane of brain capillary endothelial cells of immature rats.

Metabolic fuel and amino acid transport into the brain in experimental hypothyroidism

1990 ◽  
Vol 122 (2) ◽  
pp. 156-162 ◽  
Author(s):  
Arshag D. Mooradian
Keyword(s):  
Amino Acids ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Transport Systems ◽  
Brain Uptake ◽  
Acid Transport ◽  
Brain Extraction ◽  
Blood Brain ◽  
Brain Uptake Index ◽  
The Brain

Abstract The effect of hypothyroidism in the adult rat on blood-brain barrier and muscle transport of hexoses, neutral amino acids, basic amino acids, monocarboxylic acids, and ketone bodies was examined using single arterial injection-tissue sampling technique. The cerebral blood flow and brain extraction of 3H2O (internal reference substance) was not altered in 3-month-old hypothyroid rats maintained on methimazole, 0.025% in the drinking water, for 7 weeks. The brain uptake index of D-β-hydroxybutyrate was significantly reduced in hypothyroid rats (2.4 ± 0.3 vs 4.6 ± 0.6% p<0.001). Hypothyroid rats given thyroid hormone replacement therapy had normal brain uptake of D-β-hydroxybutyrate (4.4 ± 0.8%). The brain uptake index of butyrate was also significantly reduced in hypothyroid rats (39.3 ± 2.1 vs 47.2 ± 0.74%, p<0.001). The brain uptake index of other test substances and muscle uptake of nutrients examined were not altered in hypothyroid rats. These studies indicate that of the four transport systems examined in two tissues, the blood-brain barrier monocarboxylic acid transport system is most susceptible to the hypothyroidism-induced changes.

Modulation of p-Glycoprotein Transport Function at the Blood-Brain Barrier

2005 ◽  
Vol 230 (2) ◽  
pp. 118-127 ◽  
Author(s):  
Björn Bauer ◽  
Anika M. S. Hartz ◽  
Gert Fricker ◽  
David S. Miller
Keyword(s):  
Blood Brain Barrier ◽  
Viral Infections ◽  
Brain Barrier ◽  
Capillary Endothelium ◽  
Brain Capillary ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Junctional Permeability ◽  
Capillary Endothelial Cells ◽  
The Brain

The central nervous system (CNS) effects of many therapeutic drugs are blunted because of restricted entry into the brain. The basis for this poor permeability is the brain capillary endothelium, which comprises the blood-brain barrier. This tissue exhibits very low paracellular (tight-junctional) permeability and expresses potent, multispecific, drug export pumps. Together, these combine to limit use of pharmacotherapy to treat CNS disorders such as brain cancer and bacterial or viral infections. Of all the xenobiotic efflux pumps highly expressed in brain capillary endothelial cells, p-glycoprotein handles the largest fraction of commonly prescribed drugs and thus is an obvious target for manipulation. Here we review recent studies focused on understanding the mechanisms by which p-glycoprotein activity in the blood-brain barrier can be modulated. These include (i) direct inhibition by specific competitors, (ii) functional modulation, and (iii) transcriptional modulation. Each has the potential to specifically reduce p-glycoprotein function and thus selectively increase brain permeability of p-glycoprotein substrates.

scholarly journals Age influences susceptibility of brain capillary endothelial cells to La Crosse virus infection and cell death

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Rahul Basu ◽  
Vinod Nair ◽  
Clayton W. Winkler ◽  
Tyson A. Woods ◽  
Iain D. C. Fraser ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Virus Infection ◽  
La Crosse Virus ◽  
Brain Capillary ◽  
Adult Mice ◽  
Age Related ◽  
Capillary Endothelial Cells ◽  
The Brain

Abstract Background A key factor in the development of viral encephalitis is a virus crossing the blood-brain barrier (BBB). We have previously shown that age-related susceptibility of mice to the La Crosse virus (LACV), the leading cause of pediatric arbovirus encephalitis in the USA, was associated with the ability of the virus to cross the BBB. LACV infection in weanling mice (aged around 3 weeks) results in vascular leakage in the olfactory bulb/tract (OB/OT) region of the brain, which is not observed in adult mice aged > 6–8 weeks. Thus, we studied age-specific differences in the response of brain capillary endothelial cells (BCECs) to LACV infection. Methods To examine mechanisms of LACV-induced BBB breakdown and infection of the CNS, we analyzed BCECs directly isolated from weanling and adult mice as well as established a model where these cells were infected in vitro and cultured for a short period to determine susceptibility to virus infection and cell death. Additionally, we utilized correlative light electron microscopy (CLEM) to examine whether changes in cell morphology and function were also observed in BCECs in vivo. Results BCECs from weanling, but not adult mice, had detectable infection after several days in culture when taken ex vivo from infected mice suggesting that these cells could be infected in vitro. Further analysis of BCECs from uninfected mice, infected in vitro, showed that weanling BCECs were more susceptible to virus infection than adult BCECs, with higher levels of infected cells, released virus as well as cytopathic effects (CPE) and cell death. Although direct LACV infection is not detected in the weanling BCECs, CLEM analysis of brain tissue from weanling mice indicated that LACV infection induced significant cerebrovascular damage which allowed virus-sized particles to enter the brain parenchyma. Conclusions These findings indicate that BCECs isolated from adult and weanling mice have differential viral load, infectivity, and susceptibility to LACV. These age-related differences in susceptibility may strongly influence LACV-induced BBB leakage and neurovascular damage allowing virus invasion of the CNS and the development of neurological disease.

Receptor-mediated transcytosis of transferrin through blood-brain barrier endothelial cells

1996 ◽  
Vol 270 (4) ◽  
pp. H1149-H1158 ◽  
Author(s):  
L. Descamps ◽  
M. P. Dehouck ◽  
G. Torpier ◽  
R. Cecchelli
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Bovine Brain ◽  
Brain Barrier ◽  
Double Labeling ◽  
Brain Capillary ◽  
Brain Capillary Endothelial Cells ◽  
Blood Brain ◽  
Capillary Endothelial Cells ◽  
A Cell

A cell culture model of the blood-brain barrier consisting of a coculture of bovine brain capillary endothelial cells (BBCECs) and astrocytes has been used to examine the mechanism of iron transport to the brain. Binding experiments showed that BBCECs express 35,000 high-affinity (concn at 50% receptor saturation = 11.3 +/- 2.1 nM) transferin (Tf) receptors per cell. In contrast to apo-transferrin (apoTf) we observed a specific transport of holo-transferrin (holoTf) across BBCECs. This transport was inhibited completely at low temperature. Moreover, the anti-Tf receptor antibody (OX-26) competitively inhibited holoTf uptake by BBCECs. Pulse-chase experiments demonstrated that only 10% of Tf was recycled to the luminal side of the cells, whereas the majority of Tf was transcytosed to the abluminal side; double-labeling experiments clearly demonstrated that iron crosses BBCECs bound to Tf. No intraendothelial degradation of Tf was observed, suggesting that the intraendothelial pathway through BBCECs bypasses the lysosomal compartment. These results clearly show that the iron-Tf complex is transcytosed across brain capillary endothelial cells by a receptor-mediated pathway without any degradation.

scholarly journals The pericyte–glia interface at the blood–brain barrier

2018 ◽  
Vol 132 (3) ◽  
pp. 361-374 ◽  
Author(s):  
Patrizia Giannoni ◽  
Jerome Badaut ◽  
Cyril Dargazanli ◽  
Alexis Fayd’Herbe De Maudave ◽  
Wendy Klement ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Glial Cells ◽  
Outer Wall ◽  
Brain Barrier ◽  
Capillary Endothelium ◽  
Brain Capillary ◽  
Multicellular Structure ◽  
Blood Brain ◽  
Acute Insult ◽  
The Brain

The cerebrovasculature is a multicellular structure with varying rheological and permeability properties. The outer wall of the brain capillary endothelium is enclosed by pericytes and astrocyte end feet, anatomically assembled to guarantee barrier functions. We, here, focus on the pericyte modifications occurring in disease conditions, reviewing evidence supporting the interplay amongst pericytes, the endothelium, and glial cells in health and pathology. Deconstruction and reactivity of pericytes and glial cells around the capillary endothelium occur in response to traumatic brain injury, epilepsy, and neurodegenerative disorders, impacting vascular permeability and participating in neuroinflammation. As this represents a growing field of research, addressing the multicellular reorganization occurring at the outer wall of the blood-brain barrier (BBB) in response to an acute insult or a chronic disease could disclose novel disease mechanisms and therapeutic targets.

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