Distribution of protein, lipid and administered bromide between serum and CSF in myxedema

Schacht, Richard A.; Tourtellotte, Wallace W.; Frame, Boy; Nickel, Stewart N.

doi:10.1016/0026-0495(68)90028-0

Cited by 3 publications

(3 citation statements)

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“…Evaluation of the cerebral vessels in hypothyroid animals showed that the BBB of these animals in non-ischemic conditions were somewhat permeable to EB color and the rate of its damage after cerebral ischemia was more than that of the euthyroid animals. The result of studies on untreated hypothyroid patients showed dysfunction of the cerebral vessels in these patients as well as increased amount of proteins and other macromolecules in their cerebrospinal uid (Thompson, Thompson et al 1928, Schacht, Tourtellotte et al 1968, Nystrom, Hamberger et al 1997. Even, rare cases of papillae edema have been reported in hypothyroid patients (Frost, Lee et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Even, rare cases of papillae edema have been reported in hypothyroid patients (Frost, Lee et al 2004). Alternative treatment with thyroid hormones ameliorates this defect (Thompson, Thompson et al 1928, Schacht, Tourtellotte et al 1968). However, studies have shown that reversible BBB disruption is in uenced by factors such as duration and severity of the disease (Nystrom, Hamberger et al 1997).…”

Section: Discussionmentioning

confidence: 99%

“…BBB disruption and associated brain edema will result in more pressure on the cerebral vessels, less penumbra blood supply, and more ischemia-related damages (Dirnagl, Iadecola et al 1999). Some reports showed that untreated hypothyroidism accompanies with varying degrees of BBB damages evidenced by higher concentrations of macromolecules and cerebrospinal uid proteins in hypothyroid animals or untreated hypothyroid patients (Thompson, Thompson et al 1928, Schacht, Tourtellotte et al 1968, Nystrom, Hamberger et al 1997, Frost, Lee et al 2004. Few researches have known dysfunction of the endothelial cells and glia cells as the reason for breaking BBB (Pancotto, Rossmeisl et al 2010).…”

Section: Introductionmentioning

confidence: 99%

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Hypothyroidism Alleviates Cerebral Infarction but Exacerbates Blood-brain Barrier Disruption Following Transient Ischemic Stroke in Rats

Keshavarz

Dehghani

2021

Preprint

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Hypothyroidism is both a risk factor for stroke by disrupting fat metabolism and increasing atherosclerosis also a potential protective factor against its injuries. Hypothyroidism can influence the function of cerebral vessels such that BBB disruption is a reported complication of untreated hypothyroidism. The effects of hypothyroidism on cerebral vascular function in normal condition and following the ischemia-reperfusion is investigated in this study. Two groups of control euthyroid (CN) and hypothyroid (HPO) rats were studied. Hypothyroidism was induced by feeding methazole dissolved in drinking water (0.025 g/100 ml) for 4 weeks. After ensuring the hypothyroidism induction, cerebral ischemia-reperfusion was induced by MCAO. Following the reperfusion period, neuromotor dysfunction were evaluated and after removal of the brain, the volume of the infarct area was studied by the TTC staining and the BBB destruction was evaluated by the Evans Blue (EB) extravasation technique. Treatment with methimazole significantly reduced the levels of thyroid hormones (T3:198±4 vs.73±3µg/dl and T4: 3.08±0.07 vs.1.03±0.04µg/dl) in HPO. Furthermore, many clinical signs of hypothyroidism were developed in this group of animals. Hypothyroidism was associated with increased cerebral vascular permeability under non-ischemic conditions and exacerbation of BBB destruction after ischemia. However, neuromotor disorders and infarct volume were lower in hypothyroid animals than in euthyroid animals. Hypothyroidism has dual effects on ischemia-induced cerebrovascular damages. Aggravation of BBB destruction and alleviation of neuronal death following the cerebral ischemia-reperfusion are two converse effects of hypothyroidism. To clarify the exact mechanisms by which hypothyroidism causes these effects more investigations is required.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hypothyroidism Alleviates Cerebral Infarction but Exacerbates Blood-brain Barrier Disruption Following Transient Ischemic Stroke in Rats

Keshavarz

Dehghani

2021

Preprint

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Bypassing the brain barriers: upregulation of serum miR-495 and miR-543-3p reflects thyroid-mediated developmental neurotoxicity in the rat

O’Shaughnessy,

Sasser,

Bell

et al. 2023

Toxicological Sciences

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Evaluating the neurodevelopmental effects of thyroid disrupting chemicals is challenging. While some standardized developmental and reproductive toxicity studies recommend serum thyroxine (T4) measures in developing rats, extrapolating between a serum T4 reduction and neurodevelopmental outcomes is not straightforward. Previously, we showed that the blood-brain and blood-cerebrospinal fluid barriers may be affected by developmental hypothyroidism in newborn rats. Here, we hypothesized that if the brain barriers were functionally disturbed by abnormal thyroid action, then small molecules may escape from the brain tissue and into general circulation. These small molecules could then be identified in blood samples, serving as a direct readout of thyroid-mediated developmental neurotoxicity. To address these hypotheses, pregnant rats were exposed to propylthiouracil (PTU, 0 or 3 ppm) to induce thyroid hormone insufficiency, and dams were permitted to give birth. PTU significantly reduced serum T4 in postnatal offspring. Consistent with our hypothesis, we show that tight junctions of the brain barriers were abnormal in PTU exposed pups, and the blood-brain barrier exhibited increased permeability. Next, we performed serum microRNA sequencing (miRNA-Seq) to identify non-coding RNAs that may reflect these neurodevelopmental disturbances. Of the differentially expressed miRNAs identified, 7 were upregulated in PTU exposed pups. Validation by qRT-PCR show that miR-495 and miR-543-3p were similarly upregulated in males and females. Interestingly, these miRNAs have been linked to cell junction dysfunction in other models, paralleling the identified abnormalities in the rat brain. Taken together, these data show that miR-495 and miR-543-3p may be novel in vivo biomarkers of thyroid-mediated developmental neurotoxicity.

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Thyroid hormone action controls multiple components of cell junctions at the ventricular zone in the newborn rat brain

O’Shaughnessy

McMichael²,

Sasser³

et al. 2023

Front. Endocrinol.

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Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a periventricular heterotopia in developing rats. This heterotopia occurs in the posterior telencephalon, and its formation was preceded by loss of radial glia cell polarity. As radial glia mediate cell migration and originate in a progenitor cell niche called the ventricular zone (VZ), we hypothesized that TH action may control cell signaling in this region. Here we addressed this hypothesis by employing laser capture microdissection and RNA-Seq to evaluate the VZ during a known period of TH sensitivity. Pregnant rats were exposed to a low dose of propylthiouracil (PTU, 0.0003%) through the drinking water during pregnancy and lactation. Dam and pup THs were quantified postnatally and RNA-Seq of the VZ performed in neonates. The PTU exposure resulted in a modest increase in maternal thyroid stimulating hormone and reduced thyroxine (T4). Exposed neonates exhibited hypothyroidism and T4 and triiodothyronine (T3) were also reduced in the telencephalon. RNA-Seq identified 358 differentially expressed genes in microdissected VZ cells of hypothyroid neonates as compared to controls (q-values ≤0.05). Pathway analyses showed processes like maintenance of the extracellular matrix and cytoskeleton, cell adhesion, and cell migration were significantly affected by hypothyroidism. Immunofluorescence also demonstrated that collagen IV, F-actin, radial glia, and adhesion proteins were reduced in the VZ. Immunohistochemistry of integrin αvβ3 and isoforms of both thyroid receptors (TRα/TRβ) showed highly overlapping expression patterns, including enrichment in the VZ. Taken together, our results show that TH action targets multiple components of cell junctions in the VZ, and this may be mediated by both genomic and nongenomic mechanisms. Surprisingly, this work also suggests that the blood-brain and blood-cerebrospinal fluid barriers may also be affected in hypothyroid newborns.

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Distribution of protein, lipid and administered bromide between serum and CSF in myxedema

Cited by 3 publications

References 9 publications

Hypothyroidism Alleviates Cerebral Infarction but Exacerbates Blood-brain Barrier Disruption Following Transient Ischemic Stroke in Rats

Hypothyroidism Alleviates Cerebral Infarction but Exacerbates Blood-brain Barrier Disruption Following Transient Ischemic Stroke in Rats

Bypassing the brain barriers: upregulation of serum miR-495 and miR-543-3p reflects thyroid-mediated developmental neurotoxicity in the rat

Thyroid hormone action controls multiple components of cell junctions at the ventricular zone in the newborn rat brain

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