Blood-brain barrier permeability to sucrose and dextran after osmotic opening

Ziylan, Y. Ziya; Robinson, Philip J.; Rapoport, Stanley I.

doi:10.1152/ajpregu.1984.247.4.r634

Cited by 34 publications

(41 citation statements)

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“…Alternatively, BBB disruption lesions could have been too small to detect, with albumin having a molecular weight of about 60,000 daltons. Sucrose, with a molecular weight of 340 daltons and a radius of about 5 Å, can detect much smaller disruptions [39]. However, we found here that the BBB was intact to sucrose (table 1).…”

Section: Discussioncontrasting

confidence: 44%

Regional Variations in the Transport of Interleukin-1α across the Blood-Brain Barrier in ICR and Aging SAMP8 Mice

Moinuddin

Morley

Banks³

2000

Neuroimmunomodulation

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Objectives: The blood-brain barrier (BBB) transports blood-borne interleukin-1α (IL-1) into the brain by a saturable process. Here, we determined whether all regions of the brain could transport IL-1 and whether transport differed between ICR and SAMP8 mice, a strain which overexpresses amyloid beta protein (Aβ) with aging. Methods: We used multiple-time regression analysis to measure the unidirectional influx rate (transport rate) of radioactively labeled IL-1 for 10 brain regions in young (2 months old) ICR mice and in young and aged (17 months old) SAMP8 mice. We also used radioactively labeled sucrose and albumin to determine whether the BBB was disrupted in aged SAMP8 mice. Results: In young ICR mice, eight of the 10 brain regions transported IL-1, with the pons-medulla having the fastest transport rate (0.584 ± 0.163 µl/g·min), but no statistically significant differences occurred among regions. In SAMP8 mice, only four regions transported IL-1. In young SAMP8 mice, the pons-medulla transported IL-1 faster than any other region (0.642 ± 0.197 µl/g·min), a rate that was significantly different (p < 0.01) from each of the other regions. Aged SAMP8 mice had a similar regional transport pattern to young SAMP8 mice, but there were no statistically significant differences among the four transporting regions. Sucrose and albumin spaces were not increased in aged SAMP8 mice, demonstrating an intact BBB. Conclusions: The smaller number of regions transporting IL-1 in SAMP8 mice as compared to ICR mice demonstrates a genetic influence on transport which could alter the ability of blood-borne IL-1 to directly affect brain functions. No evidence of BBB disruption was found in the aged SAMP8 mice from this colony.

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Section: Discussioncontrasting

confidence: 44%

Regional Variations in the Transport of Interleukin-1α across the Blood-Brain Barrier in ICR and Aging SAMP8 Mice

Moinuddin

Morley

Banks³

2000

Neuroimmunomodulation

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“…It may therefore not be surprising that results on the BBB permeability window postBBBD differed from ours. 8,11,29,[37][38][39][40][41] To eliminate confounding factors, we selected two CAs having the same charge, À 2, in solution but a different weight and size to perform our study. 20 Since, other than size and molecular weight, molecular charge is also expected to have an impact on drug penetration, since the opened tight junctions are negatively charged.…”

Section: Discussionmentioning

confidence: 99%

“…The size of the injected drug determines the extent of its delivery across the permeabilized BBB. 8,19 Prior studies applied different methodologies and drug dosing, making a quantitative comparison of the gain afforded by the BBBD strategy difficult. Dynamic contrast enhanced-MRI (DCE-MRI) allows for a noninvasive and quantitative characterization of drug delivery, accumulation, and distribution in the brain.…”

Section: Introductionmentioning

confidence: 99%

Impact of Drug Size on Brain Tumor and Brain Parenchyma Delivery after a Blood–Brain Barrier Disruption

Blanchette

Tremblay

Lepage

et al. 2014

J Cereb Blood Flow Metab

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Drug delivery to the brain is influenced by the blood-brain barrier (BBB) and blood-tumor barrier (BTB) to an extent that is still debated in neuro-oncology. In this paper, we studied the delivery across the BTB and the BBB of compounds with different molecular sizes in normal and glioma-bearing rats. Studies were performed at baseline as well as after an osmotic BBB disruption (BBBD) using dynamic contrast-enhanced magnetic resonance imaging and two T 1 contrast agents (CAs), Magnevist (743 Da) and Gadomer (17,000 Da). More specifically, we determined the time window for the BBB permeability, the distribution and we calculated the brain exposure to the CAs. A different pattern of accumulation and distribution at baseline as well as after a BBBD procedure was observed for both agents, which is consistent with their different molecular size and weight. Baseline tumor exposure was threefold higher for Magnevist compared with Gadomer, whereas postBBBD tumor exposure was twofold higher for Magnevist. Our study clearly showed that the time window and the extent of delivery across the intact, as well as permeabilized BTB and BBB are influenced by drug size.

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“…The phenomenon has previously been characterized as 'osmotic opening' of the BBB when hyperosmotic substances were applied directly to the pial surface (Cserr et al, 1987b;Rapoport et al, 1972) or injected into the carotid artery (Blasberg et al, 1980;Ziylan et al, 1984). Therefore, the 'threshold' that we identified between the two lines, presumably is similar to the osmotic opening of the BBB after the application of topical substances or the intracarotid infusions (Blasberg et al, 1980;Cserr et al, 1987b;Rapoport et al, 1972;Ziylan et al, 1984). Before reaching the threshold, the glucose-induced increases in osmolality resulted in small increases (Figures 1-3) in K i such that barrier function was in the near normal range (Cserr et al, 1987b).…”

Section: Discussionmentioning

confidence: 99%

Comparative Effects of Glucose- and Mannitol-Induced Osmolar Stress on Blood—Brain Barrier Function in Ovine Fetuses and Lambs

Stonestreet

Sadowska

Hanumara

et al. 2011

J Cereb Blood Flow Metab

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We examined the effects of hyperglycemic hyperosmolality on blood-brain barrier (BBB) permeability during development. We hypothesized that the barrier becomes more resistant to hyperglycemic hyperosmolality during development, and the immature BBB is more resistant to glucose than to mannitol hyperosmolality. We quantified the BBB response to hyperosmolality with the blood-to-brain transfer constant (K i ) in immature fetuses, premature, and newborn lambs. K i increased as a function of increases in osmolality. A segmented regression model described the relationship between K i and osmolality. At lower osmolalities, changes in K i were minimal but after a threshold, increases were linear. We examined responses of K i to hyperglycemic hyperosmolality by comparing the thresholds and slopes of the second regression segments. Lower thresholds and steeper slopes indicate greater vulnerability to hyperosmolality. Thresholds increased (P < 0.05) during development in pons and superior colliculus. Thresholds were higher (P < 0.05) during glucose than mannitol hyperosmolality in thalamus, superior colliculus, inferior colliculus and medulla of premature lambs, and in cerebrum and cerebellum of newborns. We conclude that BBB permeability increased as a function of changes in glucose osmolality, the barrier becomes more resistant to glucose hyperosmolality in two brain regions during development, and the barrier is more resistant to glucose than to mannitol hyperosmolality in some brain regions of premature and newborn lambs.

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Blood-brain barrier permeability to sucrose and dextran after osmotic opening

Cited by 34 publications

References 0 publications

Regional Variations in the Transport of Interleukin-1α across the Blood-Brain Barrier in ICR and Aging SAMP8 Mice

Regional Variations in the Transport of Interleukin-1α across the Blood-Brain Barrier in ICR and Aging SAMP8 Mice

Impact of Drug Size on Brain Tumor and Brain Parenchyma Delivery after a Blood–Brain Barrier Disruption

Comparative Effects of Glucose- and Mannitol-Induced Osmolar Stress on Blood—Brain Barrier Function in Ovine Fetuses and Lambs

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