Non-invasive measurement of solute permeability in cerebral microvessels of the rat

Yuan, Wei; Lv, Yonggang; Zeng, Min; Fu, Bingmei M.

doi:10.1016/j.mvr.2008.08.004

Cited by 140 publications

(167 citation statements)

References 28 publications

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“…This range of P bEnd3 to P pia is much smaller than that of P mesentery (measured in intact rat mesenteric microvessels) to P pia , which is from 6 to 11-fold for the similar sized solutes. 19,47 Therefore, our results indicate that the bEnd3 monolayer carries the low solute permeability character of the BBB and thus can be a fairly good in vitro model for studying solute transport across the BBB.…”

Section: Resultsmentioning

confidence: 64%

“…Figure 4 compares the permeability of bEnd3 monolayer to various sized neutral solutes, NaF, dextran-4k, dextran-20k, and dextran-70k (diamonds), with that of intact rat pial microvessels to the same solutes (squares). 47 The ratios of permeability of bEnd 3 (P bEnd3 ) to that of pial microvessels (P pia ) are 3.0, 3.6, 3.8 and 3.4-fold, correspondingly, to NaF, dextran-4k, dextran-20k, and dextran-70k. This range of P bEnd3 to P pia is much smaller than that of P mesentery (measured in intact rat mesenteric microvessels) to P pia , which is from 6 to 11-fold for the similar sized solutes.…”

Section: Resultsmentioning

confidence: 98%

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Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Yuan

2010

Ann Biomed Eng

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Abstract-Charge carried by the surface glycocalyx layer (SGL) of the cerebral endothelium has been shown to significantly modulate the permeability of the blood-brain barrier (BBB) to charged solutes in vivo. The cultured monolayer of bEnd3, an immortalized mouse cerebral endothelial cell line, is becoming a popular in vitro BBB model due to its easy growth and maintenance of many BBB characteristics over repeated passages. To test whether the SGL of bEnd3 monolayer carries similar charge as that in the intact BBB and quantify this charge, which can be characterized by the SGL thickness (L f ) and charge density (C mf ), we measured the solute permeability of bEnd3 monolayer to neutral solutes and to solutes with similar size but opposite charges: negatively charged a-lactalbumin (À11) and positively charged ribonuclease (+3). Combining the measured permeability data with a transport model across the cell monolayer, we predicted the L f and the C mf of bEnd3 monolayer, which is~160 nm and~25 mEq/L, respectively. We also investigated whether orosomucoid, a plasma glycoprotein modulating the charge of the intact BBB, alters the charge of bEnd3 monolayer. We found that 1 mg/mL orosomucoid would increase SGL charge density of bEnd3 monolayer to~2-fold of its control value.

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Section: Resultsmentioning

confidence: 64%

Section: Resultsmentioning

confidence: 98%

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Yuan

2010

Ann Biomed Eng

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“…7,15,26,27 Subsequently, the MBs were injected via the carotid artery at a constant rate to achieve a constant concentration in the cerebral microvessels in the region of sonication, where the "optimal" concentration was based on previous studies. 6,7,21,28 After FUS in the presence of MBs, tetramethylrhodamine isothiocyanate (TRITC)-dextran-155 kDa, a model mAbs macromolecule, was injected via the carotid artery, and the BBB permeability was determined for an individual microvessel by a method described by Yuan et al 24 Our current study enabled us to find optimal FUS and MBs that can induce reversible increase in the BBB permeability to macromolecules. These findings will contribute to designing efficient and safe delivery strategies for the brain drug delivery, particularly for the delivery of antibodies.…”

Section: Shi Et Almentioning

confidence: 97%

“…Therefore, the BBB disruption assessed by the MRI and histological examination is more qualitative than quantitative. 23,24 To overcome aforementioned limitations, two-photon microscopy can be employed to quantitatively access the enhanced permeability of the cerebral vasculature after FUS. 25 In addition to micrometer spatial resolution, two-photon microscopy offers the advantage of deep tissue penetration, which is essential for the BBB permeability measurement.…”

Section: Shi Et Almentioning

confidence: 99%

“…23,24 Briefly, the skull in the region of interest (ROI) was exposed by shaving off the hair and cutting away the skin and connective tissue. A section of the frontoparietal bone (either left or right) was carefully ground with a high speed micro-grinder (0-50,000 rpm, DLT 50KBU; Brasseler USA, Savannah, GA, USA) until a part of it (~4 mm ×6 mm) became soft and translucent.…”

Section: Microbubble Preparationmentioning

confidence: 99%

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Quantification of transient increase of the blood–brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles

Shi

Palacio-Mancheno

Badami

et al. 2014

IJN

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Radioimmunotherapy using a radiolabeled monoclonal antibody that targets tumor cells has been shown to be efficient for the treatment of many malignant cancers, with reduced side effects. However, the blood–brain barrier (BBB) inhibits the transport of intravenous antibodies to tumors in the brain. Recent studies have demonstrated that focused ultrasound (FUS) combined with microbubbles (MBs) is a promising method to transiently disrupt the BBB for the drug delivery to the central nervous system. To find the optimal FUS and MBs that can induce reversible increase in the BBB permeability, we employed minimally invasive multiphoton microscopy to quantify the BBB permeability to dextran-155 kDa with similar molecular weight to an antibody by applying different doses of FUS in the presence of MBs with an optimal size and concentration. The cerebral microcirculation was observed through a section of frontoparietal bone thinned with a micro-grinder. About 5 minutes after applying the FUS on the thinned skull in the presence of MBs for 1 minute, TRITC (tetramethylrhodamine isothiocyanate)-dextran-155 kDa in 1% bovine serum albumin in mammalian Ringer’s solution was injected into the cerebral circulation via the ipsilateral carotid artery by a syringe pump. Simultaneously, the temporal images were collected from the brain parenchyma ~100–200 μm below the pia mater. Permeability was determined from the rate of tissue solute accumulation around individual microvessels. After several trials, we found the optimal dose of FUS. At the optimal dose, permeability increased by ~14-fold after 5 minutes post-FUS, and permeability returned to the control level after 25 minutes. FUS without MBs or MBs injected without FUS did not change the permeability. Our method provides an accurate in vivo assessment for the transient BBB permeability change under the treatment of FUS. The optimal FUS dose found for the reversible BBB permeability increase without BBB disruption is reliable and can be applied to future clinical trials.

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Triculture Model of In Vitro BBB and its Application to Study BBB‐Associated Chemosensitivity and Drug Delivery in Glioblastoma

Seo

Nah

Lee

et al. 2021

Adv Funct Materials

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Physiologically, brain tumors interact with surrounding vascular and glial cells, and change their responses to survive in brain tissue‐specific microenvironments. A major difficulty in brain tumor treatment is caused by the organism's high resistance to pharmaceutical drugs and poor blood–brain barrier (BBB) penetration. Therefore, mimicking the physiological environment of brain tumors on in vitro platforms can aid in predicting the cellular response to drugs. Here, an engineered 3D human glioblastoma in vitro platform that is integrated with a tricultured BBB is presented. First, the barrier function of the constructed BBB model and its reversibility are characterized, after administrating BBB‐opening agents through the microvasculature. The brain tumor cells that are cocultured in the BBB show a more aggressive growth pattern and high drug resistance, as well as secreting high concentrations of inflammatory cytokines. Finally, the delivery of BBB‐nonpenetrating drugs are promoted by chemically opening the BBB. The results of this study indicate that the platform can potentially study the physiology of the BBB, and monitor drug responses based on the interaction of the brain tumor and BBB.

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Non-invasive measurement of solute permeability in cerebral microvessels of the rat

Cited by 140 publications

References 28 publications

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Quantification of transient increase of the blood–brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles

Triculture Model of In Vitro BBB and its Application to Study BBB‐Associated Chemosensitivity and Drug Delivery in Glioblastoma

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Non-invasive measurement of solute permeability in cerebral microvessels of the rat

Cited by 140 publications

References 28 publications

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Quantification of transient increase of the blood&ndash;brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles

Triculture Model of In Vitro BBB and its Application to Study BBB‐Associated Chemosensitivity and Drug Delivery in Glioblastoma

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Quantification of transient increase of the blood–brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles