Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid, and the brain

SummaryBlood was injected into the brains of dogs to produce artificial haematomas, and paraffin injected to produce intracerebral paraffin masses. Cerebrospinal fluid (CSF) and peripheral blood samples were withdrawn at regular intervals and their fibrinolytic activities estimated by the fibrin plate method. Trans-form aminomethylcyclohexane-carboxylic acid (t-AMCHA) was administered to some individuals. Genera] relationships were found between changes in CSF fibrinolytic activity, area of tissue damage and survival time. t-AMCHA was clearly beneficial to those animals given a programme of administration. Tissue activator was extracted from the brain tissue after death or sacrifice for haematoma examination. The possible role of tissue activator in relation to haematoma development, and clinical implications of the results, are discussed.

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Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms20122982 ◽

2019 ◽

Vol 20 (12) ◽

pp. 2982 ◽

Cited By ~ 2

Author(s):

Gil Yong Park ◽

Angelo Jamerlan ◽

Kyu Hwan Shim ◽

Seong Soo A. An

Keyword(s):

Cerebrospinal Fluid ◽

Genetic Mutations ◽

Hormone Binding ◽

Wild Type ◽

Autonomic Motor ◽

Hormone Binding Protein ◽

The Brain ◽

Tetrameric Form

Transthyretin (TTR) is a thyroid hormone-binding protein which transports thyroxine from the bloodstream to the brain. The structural stability of TTR in tetrameric form is crucial for maintaining its original functions in blood or cerebrospinal fluid (CSF). The altered structure of TTR due to genetic mutations or its deposits due to aggregation could cause several deadly diseases such as cardiomyopathy and neuropathy in autonomic, motor, and sensory systems. The early diagnoses for hereditary amyloid TTR with cardiomyopathy (ATTR-CM) and wild-type amyloid TTR (ATTRwt) amyloidosis, which result from amyloid TTR (ATTR) deposition, are difficult to distinguish due to the close similarities of symptoms. Thus, many researchers investigated the role of ATTR as a biomarker, especially its potential for differential diagnosis due to its varying pathogenic involvement in hereditary ATTR-CM and ATTRwt amyloidosis. As a result, the detection of ATTR became valuable in the diagnosis and determination of the best course of treatment for ATTR amyloidoses. Assessing the extent of ATTR deposition and genetic analysis could help in determining disease progression, and thus survival rate could be improved following the determination of the appropriate course of treatment for the patient. Here, the perspectives of ATTR in various diseases were presented.

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High Blood Pressure Effects on the Blood to Cerebrospinal Fluid Barrier and Cerebrospinal Fluid Protein Composition: A Two-Dimensional Electrophoresis Study in Spontaneously Hypertensive Rats

International Journal of Hypertension ◽

10.1155/2013/164653 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Ibrahim González-Marrero ◽

Leandro Castañeyra-Ruiz ◽

Juan M. González-Toledo ◽

Agustín Castañeyra-Ruiz ◽

Hector de Paz-Carmona ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Choroid Plexus ◽

Protein Composition ◽

Pressure Effects ◽

Apolipoprotein A1 ◽

Spontaneously Hypertensive ◽

Barrier Disruption ◽

Cerebrospinal Fluid Proteins ◽

The Brain ◽

Cerebrospinal Fluid Protein

The aim of the present work is to analyze the cerebrospinal fluid proteomic profile, trying to find possible biomarkers of the effects of hypertension of the blood to CSF barrier disruption in the brain and their participation in the cholesterol andβ-amyloid metabolism and inflammatory processes. Cerebrospinal fluid (CSF) is a system linked to the brain and its composition can be altered not only by encephalic disorder, but also by systemic diseases such as arterial hypertension, which produces alterations in the choroid plexus and cerebrospinal fluid protein composition. 2D gel electrophoresis in cerebrospinal fluid extracted from the cistern magna before sacrifice of hypertensive and control rats was performed. The results showed different proteomic profiles between SHR and WKY, thatα-1-antitrypsin, apolipoprotein A1, albumin, immunoglobulin G, vitamin D binding protein, haptoglobin andα-1-macroglobulin were found to be up-regulated in SHR, and apolipoprotein E, transthyretin,α-2-HS-glycoprotein, transferrin,α-1β-glycoprotein, kininogen and carbonic anhidrase II were down-regulated in SHR. The conclusion made here is that hypertension in SHR produces important variations in cerebrospinal fluid proteins that could be due to a choroid plexus dysfunction and this fact supports the close connection between hypertension and blood to cerebrospinal fluid barrier disruption.

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Expression and possible role of creatine transporter in the brain and at the blood-cerebrospinal fluid barrier as a transporting protein of guanidinoacetate, an endogenous convulsant

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2008.05652.x ◽

2008 ◽

Vol 107 (3) ◽

pp. 768-778 ◽

Cited By ~ 38

Author(s):

Masanori Tachikawa ◽

Jun Fujinawa ◽

Masato Takahashi ◽

Yasuyuki Kasai ◽

Masahiro Fukaya ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Creatine Transporter ◽

The Brain

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The role of metabolites and the role of histo-hematological barriers in the regulation of body functions. (End)

Kazan medical journal ◽

10.17816/kazmj70453 ◽

1937 ◽

Vol 33 (5) ◽

pp. 523-532

Author(s):

L. S. Stern

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

General Circulation ◽

Physiological State ◽

The State ◽

The Central Nervous System ◽

The Brain ◽

Physiological Systems

Evaluation of the results obtained in the study of the effect of cerebrospinal fluid on various physiological systems is complicated by the fact that the composition of the cerebrospinal fluid depends to a large extent on the state of the blood-brain barrier, and thus reflects not only a certain physiological state of the central nervous system. There is no doubt that the metabolic products of the brain, secreted into the cerebrospinal fluid, exert their effect not only on the activity of various parts of the brain and on the coordination of their functions, but due to the rapid transition of these substances from the cerebrospinal fluid into the general circulation, they also affect as a humoral a factor on the function of other physiological systems, as it was revealed in a number of experiments carried out in recent years in our laboratories. For example, it turned out that under various influences (direct irritation of the central nervous system in experimental epilepsy, irritation of the sensory nerves associated with severe pain, traumatic shock, toxemic or chemical shock, as well as starvation, prolonged insomnia, etc.) - substances appear in the cerebrospinal fluid that affect the state and activity of the cardiovascular system, the tone of smooth muscles, the excitability of the central nervous system, etc. These are the results of the work of our employees: Zeitlin, Weiss, Harles, Voskresensky, Gromakovskaya , Bazarova, Gotsman, Komarova and others. Work in this direction continues at the present time.

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Intracranial Pressure

Mayo Clinic Critical and Neurocritical Care Board Review ◽

10.1093/med/9780190862923.003.0008 ◽

2019 ◽

pp. 69-73

Author(s):

Eelco F. M. Wijdicks ◽

William D. Freeman

Keyword(s):

Cerebrospinal Fluid ◽

Smooth Muscle ◽

Choroid Plexus ◽

Blood Cells ◽

White Blood Cells ◽

Ependymal Cells ◽

Cerebral Aqueduct ◽

Epithelial Surface ◽

The Brain ◽

Route Of Delivery

Cerebrospinal fluid (CSF) fills the subarachnoid space, spinal canal, and ventricles of the brain. CSF is enclosed within the brain by the pial layer, ependymal cells lining the ventricles, and the epithelial surface of the choroid plexus, where it is largely produced. Choroid plexus is present throughout the ventricular system with the exception of the frontal and occipital horns of the lateral ventricle and the cerebral aqueduct. The vascular smooth muscle and the epithelium of the choroid plexus receive both sympathetic and parasympathetic input. In an adult, CSF is normally acellular. A normal spinal sample may contain up to 5 white blood cells (WBCs) or red blood cells (RBCs). CSF allows for a route of delivery and removal of nutrients, hormones, and transmitters for the brain.

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Role of transthyretin in thyroxine transfer from cerebrospinal fluid to brain and choroid plexus

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00789.2005 ◽

2006 ◽

Vol 291 (5) ◽

pp. R1310-R1315 ◽

Cited By ~ 29

Author(s):

Nouhad A. Kassem ◽

Rashid Deane ◽

Malcolm B. Segal ◽

Jane E. Preston

Keyword(s):

Cerebrospinal Fluid ◽

Frontal Cortex ◽

Brain Stem ◽

Choroid Plexus ◽

Binding Protein ◽

Ventricular System ◽

Perfusion Technique ◽

Cisterna Magna ◽

Lateral Ventricles

The transport of 125I-labeled thyroxine (T4) from the cerebrospinal fluid (CSF) into brain and choroid plexus (CP) was measured in anesthetized rabbit [0.5 mg/kg medetomidine (Domitor) and 10 mg/kg pentobarbitonal sodium (Sagatal) iv] using the ventriculocisternal (V-C) perfusion technique. 125I-labeled T4 contained in artificial CSF was continually perfused into the lateral ventricles for up to 4 h and recovered from the cisterna magna. The %recovery of 125I-labeled T4 from the aCSF was 47.2 ± 5.6% ( n = 10), indicating removal of 125I-labeled T4 from the CSF. The recovery increased to 53.2 ± 6.3% ( n = 4) and 57.8 ± 14.8% ( n = 3), in the presence of 100 and 200 μM unlabeled-T4, respectively ( P < 0.05), indicating a saturable component to T4 removal from CSF. There was a large accumulation of 125I-labeled T4 in the CP, and this was reduced by 80% in the presence of 200 μM unlabeled T4, showing saturation. In the presence of the thyroid-binding protein transthyretin (TTR), more 125I-labeled T4 was recovered from CSF, indicating that the binding protein acted to retain T4 in CSF. However, 125I-labeled T4 uptake into the ependymal region (ER) of the frontal cortex also increased by 13 times compared with control conditions. Elevation was also seen in the hippocampus (HC) and brain stem. Uptake was significantly inhibited by the presence of endocytosis inhibitors nocodazole and monensin by > 50%. These data suggest that the distribution of T4 from CSF into brain and CP is carrier mediated, TTR dependent, and via RME. These results support a role for TTR in the distribution of T4 from CSF into brain sites around the ventricular system, indicating those areas involved in neurogenesis (ER and HC).

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