THE INFLUENCE OF CARBON DIOXIDE INHALATION ON THE CEREBRAL VASCULAR PERMEABILITY TO TRYPAN BLUE (‘THE BLOOD-BRAIN BARRIER’)

Abstract The carbon dioxide laser has recently received clinical acceptance in neurosurgical practice. There are, however, few studies reported in the neurosurgical literature, either clinical or experimental, concerning its safety or efficacy on a physiological level by comparison to a more conventional tool. This study is not a description of a surgical technique, but is rather a basic physiological comparison of two surgical instruments. In this study, 11 cats were pretreated with the protein-bound dye, Evans blue. A corticotomy was performed in one hemisphere with the carbon dioxide laser and in the other with a microbipolar coagulator and a sharp blade. The subsequent extravasation of dye was presumed to be proportional to the amount of blood-brain barrier disruption associated with each lesion. When effective power settings for the two devices were compared, the laser lesions had significantly less extravasation of blue dye. This indicated that there was less damage to the blood-brain barrier surrounding laser corticotomy than surrounding conventional bipolar coagulation and sharp dissection at comparable power settings for each modality.

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Engineered human blood–brain barrier microfluidic model for vascular permeability analyses

Nature Protocols ◽

10.1038/s41596-021-00635-w ◽

2022 ◽

Author(s):

Cynthia Hajal ◽

Giovanni S. Offeddu ◽

Yoojin Shin ◽

Shun Zhang ◽

Olga Morozova ◽

...

Keyword(s):

Vascular Permeability ◽

Blood Brain Barrier ◽

Human Blood ◽

Brain Barrier ◽

Blood Brain

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Anti-Nogo-A antibodies prevent vascular leakage and act as pro-angiogenic factors following stroke

Scientific Reports ◽

10.1038/s41598-019-56634-1 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 5

Author(s):

Ruslan Rust ◽

Rebecca Z. Weber ◽

Lisa Grönnert ◽

Geertje Mulders ◽

Michael A. Maurer ◽

...

Keyword(s):

Vascular Permeability ◽

Blood Brain Barrier ◽

Neurite Growth ◽

Brain Barrier ◽

Vascular Repair ◽

Blood Brain Barrier Disruption ◽

Vascular Regeneration ◽

Blood Brain ◽

Brain Barrier Disruption ◽

Endothelial Growth Factor

AbstractAngiogenesis is a key restorative process following stroke but has also been linked to increased vascular permeability and blood brain barrier (BBB) disruption. Previous pre-clinical approaches primarily focused on the administration of vascular endothelial growth factor (VEGF) to promote vascular repair after stroke. Although shown to improve angiogenesis and functional recovery from stroke, VEGF increased the risk of blood brain barrier disruption and bleedings to such an extent that its clinical use is contraindicated. As an alternative strategy, antibodies against the neurite growth inhibitory factor Nogo-A have recently been shown to enhance vascular regeneration in the ischemic central nervous system (CNS); however, their effect on vascular permeability is unknown. Here, we demonstrate that antibody-mediated Nogo-A neutralization following stroke has strong pro-angiogenic effects but does not increase vascular permeability as opposed to VEGF. Moreover, VEGF-induced vascular permeability was partially prevented when VEGF was co-administered with anti-Nogo-A antibodies. This study may provide a novel therapeutic strategy for vascular repair and maturation in the ischemic brain.

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R-CHOP preceded by blood-brain barrier permeabilization with engineered tumor necrosis factor-α in primary CNS lymphoma

Blood ◽

10.1182/blood.2019000633 ◽

2019 ◽

Vol 134 (3) ◽

pp. 252-262 ◽

Cited By ~ 15

Author(s):

Andrés J. M. Ferreri ◽

Teresa Calimeri ◽

Gian Marco Conte ◽

Dario Cattaneo ◽

Federico Fallanca ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Vascular Permeability ◽

Blood Brain Barrier ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Brain Barrier ◽

Emission Computed Tomography ◽

Blood Brain ◽

Factor Α ◽

Necrosis Factor

Abstract Patients with primary central nervous system lymphoma (PCNSL) are treated with high-dose methotrexate-based chemotherapy, which requires hospitalization and extensive expertise to manage related toxicity. The use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could overcome these difficulties, but blood-brain barrier (BBB) penetration of related drugs is poor. Tumor necrosis factor-α coupled with NGR (NGR-hTNF), a peptide targeting CD13+ vessels, induces endothelial permeabilization and improves tumor access of cytostatics. We tested the hypothesis that NGR-hTNF can break the BBB, thereby improving penetration and activity of R-CHOP in patients with relapsed/refractory PCNSL (NCT03536039). Patients received six R-CHOP21 courses, alone at the first course and preceded by NGR-hTNF (0.8 μg/m2) afterward. This trial included 2 phases: an “explorative phase” addressing the effect of NGR-hTNF on drug pharmacokinetic parameters and on vessel permeability, assessed by dynamic contrast-enhanced magnetic resonance imaging and 99mTc-diethylene-triamine-pentacetic acid–single-photon emission computed tomography, and the expression of CD13 on tumor tissue; and an “expansion phase” with overall response rate as the primary end point, in which the 2-stage Simon Minimax design was used. At the first stage, if ≥4 responses were observed among 12 patients, the study accrual would have continued (sample size, 28). Herein, we report results of the explorative phase and the first-stage analysis (n = 12). CD13 was expressed in tumor vessels of all cases. NGR-hTNF selectively increased vascular permeability in tumoral/peritumoral areas, without interfering with drug plasma/cerebrospinal fluid concentrations. The NGR-hTNF/R-CHOP combination was well tolerated: there were only 2 serious adverse events, and grade 4 toxicity was almost exclusively hematological, which were resolved without dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with 9 confirmed responses (75%; 95% confidence interval, 51-99), 8 of which were complete. In conclusion, NGR-hTNF/R-CHOP was safe in these heavily pretreated patients. NGR-hTNF enhanced vascular permeability specifically in tumoral/peritumoral areas, which resulted in fast and sustained responses.

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Influence d'un retard de croissance sur la perméabilité de la barrière hémato-encéphalique chez le rat nouveau-né exposé au plomb

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y84-023 ◽

1984 ◽

Vol 62 (1) ◽

pp. 142-145 ◽

Cited By ~ 3

Author(s):

John Turnbull ◽

Jules Brodeur

Keyword(s):

Blood Brain Barrier ◽

Growth Retardation ◽

Trypan Blue ◽

Normal Diet ◽

Brain Barrier ◽

Free Access ◽

Postnatal Maturation ◽

Young Rats ◽

Nutritional Effect ◽

Blood Brain

Postnatal administration of lead to young rats via maternal milk increases the permeability of the blood–brain barrier to trypan blue. However, since this regimen delays postnatal maturation, the question arises whether growth retardation per se could explain the altered permeability to the dye. The present investigation was undertaken to examine this possibility. A first group of newborn rats were fed by dams having free access to normal food; a second group was fed by dams receiving 3% lead as the acetate salt in their food; a third group was fed by dams whose normal diet was restricted to the amount taken daily by dams of the second group. Signs of encephalopathy as shown by urinary incompetence and hind-limb paralysis were observed only in young pups exposed to lead; similarly, only the latter showed increased brain permeability to trypan blue. These results suggest that the altered permeability of the blood–brain barrier in young rats is the direct consequence of lead toxicity and not of growth retardation secondary to a nutritional effect of lead.

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Vascular permeability in the peripheral autonomic and somatic nervous systems: Controversial aspects and comparisons with the blood-brain barrier

Microscopy Research and Technique ◽

10.1002/(sici)1097-0029(19961001)35:2<122::aid-jemt3>3.0.co;2-s ◽

1996 ◽

Vol 35 (2) ◽

pp. 122-136 ◽

Cited By ~ 23

Author(s):

J.A. Kiernan

Keyword(s):

Vascular Permeability ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Nervous Systems ◽

Blood Brain

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Protein Kinase C Activation Modulates Reversible Increase in Cortical Blood–Brain Barrier Permeability and Tight Junction Protein Expression during Hypoxia and Posthypoxic Reoxygenation

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2010.119 ◽

2010 ◽

Vol 30 (11) ◽

pp. 1847-1859 ◽

Cited By ~ 70

Author(s):

Colin L Willis ◽

Diana S Meske ◽

Thomas P Davis

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Protein Expression ◽

Tight Junction ◽

Vascular Permeability ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Kinase C ◽

Blood Brain ◽

Junction Protein

Hypoxia (Hx) is a component of many disease states including stroke. Ischemic stroke occurs when there is a restriction of cerebral blood flow and oxygen to part of the brain. During the ischemic, and subsequent reperfusion phase of stroke, blood–brain barrier (BBB) integrity is lost with tight junction (TJ) protein disruption. However, the mechanisms of Hx and reoxygenation (HR)-induced loss of BBB integrity are not fully understood. We examined the role of protein kinase C (PKC) isozymes in modifying TJ protein expression in a rat model of global Hx. The Hx (6% O2) induced increased hippocampal and cortical vascular permeability to 4 and 10 kDa dextran fluorescein isothiocyanate (FITC) and endogenous rat-IgG. Cortical microvessels revealed morphologic changes in nPKC-θ distribution, increased nPKC-θ and aPKC-ζ protein expression, and activation by phosphorylation of nPKC-θ (Thr538) and aPKC-ζ (Thr410) residues after Hx treatment. Claudin-5, occludin, and ZO-1 showed disrupted organization at endothelial cell margins, whereas Western blot analysis showed increased TJ protein expression after Hx. The PKC inhibition with chelerythrine chloride (5 mg/kg intraperitoneally) attenuated Hx-induced hippocampal vascular permeability and claudin-5, PKC (θ and ζ) expression, and phosphorylation. This study supports the hypothesis that nPKC-θ and aPKC-ζ signaling mediates TJ protein disruption resulting in increased BBB permeability.

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