Age dependent contribution of entry via the CSF to the overall brain entry of small and large hydrophilic markers

Qiu, Fiona; Huang, Yifan; Saunders, Norman; Habgood, Mark D.; Dzięgielewska, Katarzyna M.

doi:10.1186/s12987-022-00387-z

Cited by 7 publications

(4 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other typical plasma proteins we found in the cystic fluids, haptoglobin, fibrinogen, transferrin, and alpha 2-macroglobulin can also be produced by the brain itself [ 40 ]. However, the contribution of local production to the CSF levels of these proteins compared to the amount of the same proteins derived from plasma is minimal [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors

Magrassi

Brambilla

Viganò

et al. 2023

Cancers

View full text Add to dashboard Cite

Cystic formation in human primary brain tumors is a relatively rare event whose incidence varies widely according to the histotype of the tumor. Composition of the cystic fluid has mostly been characterized in samples collected at the time of tumor resection and no indications of the evolution of cystic content are available. We characterized the evolution of the proteome of cystic fluid using a bottom-up proteomic approach on sequential samples obtained from secretory meningioma (SM), cystic schwannoma (CS) and cystic high-grade glioma (CG). We identified 1008 different proteins; 74 of these proteins were found at least once in the cystic fluid of all tumors. The most abundant proteins common to all tumors studied derived from plasma, with the exception of prostaglandin D2 synthase, which is a marker of cerebrospinal fluid origin. Overall, the protein composition of cystic fluid obtained at different times from the same tumor remained stable. After the identification of differentially expressed proteins (DEPs) and the protein–protein interaction network analysis, we identified the presence of tumor-specific pathways that may help to characterize tumor–host interactions. Our results suggest that plasma proteins leaking from local blood–brain barrier disruption are important contributors to cyst fluid formation, but cerebrospinal fluid (CSF) and the tumor itself also contribute to the cystic fluid proteome and, in some cases, as with immunoglobulin G, shows tumor-specific variations that cannot be simply explained by differences in vessel permeability or blood contamination.

show abstract

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors

Magrassi

Brambilla

Viganò

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…CSF/serum IGF-1 ratio, is fairly constant over the first 3-days studied here. Moreover, the uptake of rhIGF-1/rhIGFBP-3 is correlated with the activation of the IGF-1R, as displayed by increased pPKB and pERK1/2 following rhIGF-1/rhIGFBP-3 treatment at 0 h. Therefore, it could be speculated that the higher absolute concentration of IGF-1 in the CSF is dependent on both the binding to the IGF-1R in the ChP, and a putative increased serum concentration driven diffusion rate or transcellular translocation in the blood-CSF barrier in 0 h treated pups [ 35 , 36 ]. The translocation of IGF-1 through the ChP to the CSF has indeed been described to involve the IGF-1R [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3

Ortenlöf

Vallius

Karlsson

et al. 2023

Fluids Barriers CNS

View full text Add to dashboard Cite

Insulin-like growth factor-1 (IGF-1) is essential for normal brain development and regulates essential processes of vascular maturation and stabilization. Importantly, preterm birth is associated with reduced serum levels of IGF-1 as compared to in utero levels. Using a preterm rabbit pup model, we investigated the uptake of systemic recombinant human (rh) IGF-1 in complex with its main binding protein IGF-binding protein 3 (BP-3) to the brain parenchyma via the choroid plexus. Five hours after subcutaneous administration, labeled rhIGF-1/rhIGFBP-3 displayed a widespread presence in the choroid plexus of the lateral and third ventricle, however, to a less degree in the fourth, as well as in the perivascular and subarachnoid space. We found a time-dependent uptake of IGF-1 in cerebrospinal fluid, decreasing with postnatal age, and a translocation of IGF-1 through the choroid plexus. The impact of systemic rhIGF-1/rhIGFBP-3 on IGF-1 receptor activation in the choroid plexus decreased with postnatal age, correlating with IGF-1 uptake in cerebrospinal fluid. In addition, choroid plexus gene expression was observed to increase with postnatal age. Moreover, using choroid plexus in vitro cell cultures, gene expression and protein synthesis were further investigated upon rhIGF-1/rhIGFBP-3 stimulation as compared to rhIGF-1 alone, and found not to be differently altered. Here, we characterize the uptake of systemic rhIGF-1/rhIGFBP-3 to the preterm brain, and show that the interaction between systemic rhIGF-1/rhIGFBP-3 and choroid plexus varies over time.

show abstract

“…were not taken into account in the present study. Vascular space in the rat brain from E16 to adult has been reported to be around 2-4% (Toll et al 2021;Qiu et al 2022). This is particularly important in experiments where entry of drugs into the brain is low.…”

Section: Limitations Of the Studymentioning

confidence: 99%

Entry of cannabidiol into the fetal, postnatal and adult rat brain.

et al. 2023

Preprint

View full text Add to dashboard Cite

Cannabidiol is a major component of cannabis but without known psychoactive properties. A wide range of properties have been attributed to it, such as anti-inflammatory, analgesic, anti-cancer, anti-seizure and anxiolytic. However, being a fairly new compound in its purified form, little is known about cannabidiol brain entry, especially during development. Sprague Dawley rats at four developmental ages: embryonic day E19, postnatal day P4 and P12 and non-pregnant adult females were administered intraperitoneal cannabidiol at 10 mg/kg with [3H] labelled cannabidiol. To investigate the extent of placental transfer the drug was injected intravenously into E19 pregnant dams. Levels of [3H]-cannabidiol in blood plasma, cerebrospinal fluid and brain were estimated by liquid scintillation counting. Plasma protein binding of cannabidiol was identified by polyacrylamide gel electrophoresis and its bound and unbound fractions measured by ultrafiltration. Using available RNA-sequencing datasets of E19 rat brain, choroid plexus and placenta, as well as P5 and adult brain and choroid plexus, expression of 13 main cannabidiol receptors was analysed. Results showed that cannabidiol rapidly entered both the developing and adult brains. Entry into CSF was more limited. Its transfer across the placenta was substantially restricted as only about 50% of maternal blood plasma cannabidiol concentration was detected in fetal plasma. Albumin was the main, but not exclusive, cannabidiol binding protein at all ages. Several transcripts for cannabidiol receptors were expressed in age- and tissue-specific manner indicating that cannabidiol may have different functional effects in the fetal compared to adult brain.

show abstract

Age dependent contribution of entry via the CSF to the overall brain entry of small and large hydrophilic markers

Cited by 7 publications

References 52 publications

Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors

Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors

Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3

Entry of cannabidiol into the fetal, postnatal and adult rat brain.

Contact Info

Product

Resources

About