Horseradish peroxidase retention and washout in blood-brain barrier lesions

Stewart, Patricia A.; Farrell, Catherine; Farrell, Catherine L.; Hayakawa, Eiji

doi:10.1016/0165-0270(92)90125-w

Cited by 23 publications

(15 citation statements)

References 16 publications

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“…The focus of this study is three fold: (1) to investigate delivery dynamics of macromolecules and NPs, (2) to determine acute and sub-acute temporal delivery profiles, and (3) to examine sex dependence for delivery of these therapeutic agents. To examine the potential delivery of the macromolecules, a large molecular weight (MW) tracer, horseradish peroxidase (HRP, 40 kDa), was used as a surrogate [36][37][38] . Each cohort received intravenous HRP injection 10 mins prior to sacrifice at 3 h, 24 h, 3 d, 7 d following CCI injury.…”

Section: Resultsmentioning

confidence: 99%

Sex-dependent macromolecule and nanoparticle delivery in experimental brain injury

Bharadwaj

Copeland

Mathew

et al. 2019

Preprint

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Development of effective therapeutics for brain disorders is challenging, in particular, the blood-brain barrier (BBB) severely limits access of the therapeutics into the brain parenchyma. Traumatic brain injury (TBI) may lead to transient BBB permeability that affords a unique opportunity for therapeutic delivery via intravenous administration ranging from macromolecules to nanoparticles (NP) for developing precision therapeutics. In this regard, we address critical gaps in understanding the range/size of therapeutics, delivery window(s), and moreover the potential impact of biological factors for optimal delivery parameters. Here we show, for the first time, to the best of our knowledge, that 24 h post-focal TBI female mice exhibit a heightened macromolecular tracer and NP accumulation compared to male mice, indicating sexdependent differences in BBB permeability. Furthermore, we report for the first time the potential to deliver NP-based therapeutics within 3 d after focal injury in both female and male mice. The delineation of injury-induced BBB permeability with respect to sex and temporal profile is essential to more accurately tailor time-dependent precision and personalized nanotherapeutics.

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Section: Resultsmentioning

confidence: 99%

Sex-dependent macromolecule and nanoparticle delivery in experimental brain injury

Bharadwaj

Copeland

Mathew

et al. 2019

Preprint

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“…Five minutes after the pentobarbital injection, animals were injected transcardially with a solution of type VI horseradish peroxidase (HRP) (Sigma) (30 mg/ml dissolved in Evans blue 2% in 0.9% saline to provide 100 mg/kg) as previously described. 20 The brain was removed less than 1 minute later and fixed by immersion in glutaraldehyde (2.5% in PBS). Coronal sections were then incubated with 3-3Ј diaminobenzidine tetrahydrochloride (Vector Laboratories, Burlingame, CA) and hydrogen peroxide according to the manufacturer's instructions.…”

Section: Evaluation Of Blood-brain Barrier Leakagementioning

confidence: 99%

“…In the brains of uninfected mice as well as in those of mice sacrificed 5 minutes and 1 hour after inoculation, HRP was confined to the lumen of the cerebral blood vessels ( Figure 5) except in the median eminence, an area where the vessels are known to be highly permeable 20 (this was used as an internal control for our experiments). In the mouse sacrificed 6 hours after inoculation, only one HRP extravasation site could be visualized among five brain sections studied.…”

Section: State Of the Bbb Associated With C Neoformans Crossingmentioning

confidence: 99%

Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier

Charlier

Chrétien

Baudrimont

et al. 2005

The American Journal of Pathology

187

190

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Cryptococcus neoformans is a yeast responsible for disseminated meningoencephalitis in patients with cellular immune defects. The major virulence factor is the polysaccharide capsule. We took advantage of a relevant murine model of disseminated meningoencephalitis to study the early events associated with blood-brain barrier (BBB) crossing. Mice were sacrificed at 1, 6, 24, and 48 hours post-intravenous inoculation, and classical histology, electron microscopy, and double immunofluorescence were used to study tissues and yeasts. Crossing of the BBB occurred early after inoculation, did not involve the choroid plexus but instead occurred at the level of the cortical capillaries, and caused early and severe damage to the structure of the microvessels. Seeding of the leptomeninges was not the primary event but occurred secondary to leakage of cortical pseudocysts. Organ invasion was associated with changes in cryptococcal capsule structure and cell size, which differed in terms of magnitude and kinetics, depending on both the organs involved, and potentially, on the bed structure of the local capillary. The rapid changes in capsule structure could contribute to inability of the host immune response to control cryptococcal infection in extrapulmonary spaces.

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“…The molecular size of HRP (40 kd) is similar to those of serum proteins, and this similarity has been taken advantage of in a widely used method for detection of BBB breakdown. 20 The Griffonia simplicifolia isolectin B 4 (GS lectin), which labels ␣-D galactose residues, was used to visualize microglia and macrophages. GS lectin histochemistry was performed as previously described.…”

Section: Preparation Of Retinal Whole Mounts Horseradish Peroxidase mentioning

confidence: 99%

Breakdown of the Blood-Retinal Barrier Induced by Activated T Cells of Nonneural Specificity

Pollard

Chan‐Ling

2000

The American Journal of Pathology

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The cellular and microvascular responses of JC Lewis rats to an intravenous injection of activated T cells specific for ovalbumin were examined with the retinal whole mount technique. The retina was examined at various times post-injection (pi) with the use of antibodies to the ␣␤ T cell receptor (TCR) or to major histocompatibility complex class II (MHC II), the monoclonal antibody ED1, and intravascular tracers. By 12 hours pi, small numbers of TCR ؉ , ED1 ؉ , and MHC II ؉ cells were present within the lumen of retinal vessels, and minor breakdown of the blood-retinal barrier (BRB) and microglial activation were evident. The intensity of these responses had increased by 1 day pi, when small numbers of TCR ؉ cells had also undergone extravasation. By 2 to 3 days pi, the numbers of TCR ؉ , ED1 ؉ , and MHC II ؉ cells in the retinal parenchyma had increased, but the BRB breakdown and microglial activation had subsided.

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Horseradish peroxidase retention and washout in blood-brain barrier lesions

Cited by 23 publications

References 16 publications

Sex-dependent macromolecule and nanoparticle delivery in experimental brain injury

Sex-dependent macromolecule and nanoparticle delivery in experimental brain injury

Capsule Structure Changes Associated with Cryptococcus neoformans Crossing of the Blood-Brain Barrier

Breakdown of the Blood-Retinal Barrier Induced by Activated T Cells of Nonneural Specificity

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