Simple Quantitative Evaluation of Blood-Brain Barrier Disruption in Vasogenic Brain Edema

Ikeda, Yukio; Wang, M.; Nakazawa, Shozo

doi:10.1007/978-3-7091-9334-1_31

Cited by 8 publications

(9 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[35][36][37] EB is a convenient, simple dye to administer and quantify; however, it binds to serum albumin, making it a 70-kDa protein, which is considered a large molecule, and may ultimately make the use of EB a ''crude'' estimate of vascular permeability. 31,32 Previous studies have used horseradish peroxidase, which is approximately 45 kDa, or a-aminoisobutyric acid, which is only 0.1 kDa. In comparison, EB assays may be less sensitive to detecting subtle disruptions to the BSCB, because it may be too large to leak out.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Vascular Disruption and Blood–Spinal Cord Barrier Permeability following Traumatic Spinal Cord Injury

Figley

Khosravi

Legasto

et al. 2014

Journal of Neurotrauma

212

145

View full text Add to dashboard Cite

Significant vascular changes occur subsequent to spinal cord injury (SCI), which contribute to progressive pathophysiology. In the present study, we used female Wistar rats (300-350 g) and a 35-g clip-compression injury at T6 to T7 to characterize the spatial and temporal vascular changes that ensue post-SCI. Before sacrifice, animals were injected with vascular tracing dyes (2% Evans Blue (EB) or fluorescein isothiocyanate/Lycopersicon esculentum agglutinin [FITC-LEA]) to assess blood-spinal cord barrier (BSCB) integrity or vascular architecture, respectively. Spectrophotometry of EB tissue showed maximal BSCB disruption at 24 h postinjury, with significant disruption observed until 5 days postinjury (p<0.01). FITC-LEA-identified functional vasculature was dramatically reduced by 24 h. Similarly, RECA-1 immunohistochemistry showed a significant decrease in the number of vessels at 24 h postinjury, compared to uninjured animals (p<0.01), with slight increases in endogenous revascularization by 10 days postinjury. White versus gray matter (GM) quantification showed that GM vessels are more susceptible to SCI. Finally, we observed an endogenous angiogenic response between 3 and 7 days postinjury: maximal endothelial cell proliferation was observed at day 5. These data indicate that BSCB disruption and endogenous revascularization occur at specific time points after injury, which may be important for developing effective therapeutic interventions for SCI.

show abstract

Section: Discussionmentioning

confidence: 99%

“…31,32 EB was allowed to circulate for 20-30 min, and then animals were transcardially perfused with 180 mL of sterile saline. Perfusion of fluid was administered at a rate of 60 mL/min, which is only slightly lower than physiological flow rates, because we did not want to induce vascular injury during this procedure.…”

mentioning

confidence: 99%

Characterization of Vascular Disruption and Blood–Spinal Cord Barrier Permeability following Traumatic Spinal Cord Injury

Figley

Khosravi

Legasto

et al. 2014

Journal of Neurotrauma

212

145

View full text Add to dashboard Cite

show abstract

“…Preliminary experiments have shown that CHX causes little change in the normal brain because CHX is not expected to penetrate the intact BBB. Therefore, cold‐injured brain was employed as a BBB impaired model in the present study 15 . In brief, male Fischer 344 rats weighing 220–250 g were anesthetized with a mixture of ketamine hydrochloride, xylazine and ethanol.…”

Section: Methodsmentioning

confidence: 99%

“…A cold injury was induced by applying a copper rod (5 mm in diameter), cooled by liquid nitrogen, to the exposed right parietal bone for 60 s. The CHX doses administered in vivo were decided based on the report of Ijiri and Potten 10 . CHX (1 mg/animal) was administered intraperitoneally ( n = 5) at 1 h after cold injury (when BBB breakdown took place) 15 . Rats were killed with ether and their brains were removed 24 h after CHX administration.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, cold-injured brain was employed as a BBB impaired model in the present study. 15 In brief, male Fischer 344 rats weighing 220-250 g were anesthetized with a mixture of ketamine hydrochloride, xylazine and ethanol. A cold injury was induced by applying a copper rod (5 mm in diameter), cooled by liquid nitrogen, to the exposed right parietal bone for 60 s. The CHX doses administered in vivo were decided based on the report of Ijiri and Potten.…”

Section: Blood-brain Barrier (Bbb) Impaired Animal Modelmentioning

confidence: 99%

See 1 more Smart Citation

Cycloheximide induces apoptosis of astrocytes

Tsuchida

Kato

Yamada

et al. 2002

Pathology International

View full text Add to dashboard Cite

Cultured rat astrocytes were incubated in the presence of cycloheximide (CHX; 20 microg/mL), a potent neuroprotective agent. Then cells were subjected to DNA gel electrophoresis. Electrophoresis showed DNA ladder formation, which is characteristic of apoptosis. Inhibitors of interleukin-1beta-converting enzyme (ICE) and caspase 32(CPP32), which play critical roles in certain apoptotic pathways, did not block the cycloheximide-induced apoptosis of cultured astrocytes. This observation indicates that the role of ICE and CPP32 is not significant in the CHX-induced astrocyte apoptosis process. When the blood-brain barrier was disrupted in the rat, the number of brain cells undergoing apoptosis was significantly higher after cycloheximide administration, in contrast to controls. Of the cells that produced glial fibrillary acidic protein, some were observed to undergo apoptosis. Although CHX has been shown to be useful as a neuroprotective agent against ischemic neuronal death, astroglial toxicity may be problematic, depending on CHX concentration. Therefore, a prudent use of this compound is recommended.

show abstract

Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age-Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury

Vawda

Badner

Hong

et al. 2019

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Localized vascular disruption after traumatic spinal cord injury (SCI) triggers a cascade of secondary events, including inflammation, gliosis, and scarring, that can further impact recovery. In addition to immunomodulatory and neurotrophic properties, mesenchymal stromal cells (MSCs) possess pericytic characteristics. These features make MSCs an ideal candidate for acute cell therapy targeting vascular disruption, which could reduce the severity of secondary injury, enhance tissue preservation and repair, and ultimately promote functional recovery. A moderately severe cervical clip compression/contusion injury was induced at C7‐T1 in adult female rats, followed by an intravenous tail vein infusion 1 hour post‐SCI of (a) term‐birth human umbilical cord perivascular cells (HUCPVCs); (b) first‐trimester human umbilical cord perivascular cells (FTM HUCPVCs); (c) adult bone marrow mesenchymal stem cells; or (d) vehicle control. Weekly behavioral testing was performed. Rats were sacrificed at 24 hours or 10 weeks post‐SCI and immunohistochemistry and ultrasound imaging were performed. Both term and FTM HUCPVC‐infused rats displayed improved ( p < .05) grip strength compared with vehicle controls. However, only FTM HUCPVC‐infusion led to significant weight gain. All cell infusion treatments resulted in reduced glial scarring ( p < .05). Cell infusion also led to increased axonal, myelin, and vascular densities ( p < .05). Although post‐traumatic cavity volume was reduced with cell infusion, this did not reach significance. Taken together, we demonstrate selective long‐term functional recovery alongside histological improvements with HUCPVC infusion in a clinically relevant model of cervical SCI. Our findings highlight the potential of these cells for acute therapeutic intervention after SCI.

show abstract

Simple Quantitative Evaluation of Blood-Brain Barrier Disruption in Vasogenic Brain Edema

Cited by 8 publications

References 4 publications

Characterization of Vascular Disruption and Blood–Spinal Cord Barrier Permeability following Traumatic Spinal Cord Injury

Characterization of Vascular Disruption and Blood–Spinal Cord Barrier Permeability following Traumatic Spinal Cord Injury

Cycloheximide induces apoptosis of astrocytes

Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age-Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury

Contact Info

Product

Resources

About