ArticleFluids and barriers of the CNS2022
Age dependent contribution of entry via the CSF to the overall brain entry of small and large hydrophilic markers.
Article in Fluids and barriers of the CNS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 12 citations in OpenAlex.
- Effects of valproate on the entry of inert hydrophilic markers and expression of tight junction associated genes in the neonatal brain and choroid plexus of a rat model of epilepsy (GAERS).Fluids and barriers of the CNS · 2025Article
- Paracetamol, its metabolites, and their transfer between maternal circulation and fetal brain in mono- and combination therapies.Pharmacological reports : PR · 2025Article
- Entry of cannabidiol into the fetal, postnatal and adult rat brain.Cell and tissue research · 2024Article
- Characterization of choroid plexus in the preterm rabbit pup following subcutaneous administration of recombinant human IGF-1/IGFBP-3.Fluids and barriers of the CNS · 2023Article
- Proteomic Analysis on Sequential Samples of Cystic Fluid Obtained from Human Brain Tumors.Cancers · 2023Article
- Gold nanoparticle-enhanced X-ray microtomography of the rodent reveals region-specific cerebrospinal fluid circulation in the brain.Nature communications · 2023Article
- Entry of the antipsychotic drug, olanzapine, into the developing rat brain in mono- and combination therapies.F1000Research · 2022Article
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5 authors at 1 institution in 1 country.
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Abstract
backgroundApparent permeability of the blood brain barrier to hydrophilic markers has been shown to be higher in the developing brain. Apart from synthesis in situ, any substance detected in the brain parenchyma can originate from two sources: directly through blood vessels of brain vasculature and/or indirectly by entry from the cerebrospinal fluid (CSF) after transfer across the choroid plexuses. The relative quantitative contribution of these two routes to the overall brain entry remains unclear.
methodsIn rats at embryonic day 16, 19 and postnatal day 4 and young adults, a small (sucrose, mw. 342 Da) or a large (dextran, mw. 70 kDa) radiolabelled hydrophilic marker was injected intravenously for very short periods of time (30 s to 5 min) before collection of plasma, cerebrospinal fluid (CSF) and brain samples. Results are presented as concentration ratios between radioactivity measured in CSF or brain and that in plasma (%).
resultsThe dextran brain/plasma ratio five minutes post injection was similar (2-4%) from E16 to adulthood whereas the sucrose brain/plasma ratio was significantly higher in fetal brains, but was comparable to dextran values in the adult. Sucrose CSF/plasma ratios were also significantly higher in fetal animals and decreased with age. In very short experiments involving fetal animals, entry of sucrose into the CSF after only 30 s was similar to that of dextran and both markers showed similar brain/plasma ratios.
conclusionsIn the developing brain the apparent higher brain entry of a small hydrophilic marker such as sucrose can be attributed to its higher entry into the CSF and subsequent diffusion into the brain. By contrast, movement of a larger marker like 70 kDa dextran is restricted firstly by choroid plexus epithelial tight junctions and secondly by specialised junctions in the neuroependymal interface between the CSF and brain. Brain/plasma ratios of 70 kDa dextran were similar in fetal and adult rats. Therefore 70 kDa dextran should be considered an appropriate marker if brain residual vascular space is to be measured, especially in younger animals.
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