Perfluorocarbon Emulsions Improve Cognitive Recovery After Lateral Fluid Percussion Brain Injury in Rats

Zhou, Zheng; Sun, Dong; Levasseur, Joseph E.; Merenda, Amedeo; Hamm, Robert J.; Zhu, Jiepei; Spiess, Bruce D.; Bullock, M. Ross

doi:10.1227/01.neu.0000325493.51900.53

Cited by 30 publications

(33 citation statements)

References 52 publications

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“…Oxycyte is a 60% emulsion of perfluoro-tert-butylcyclohexane with phospholipid emulsifiers. In several large and small animal models, PFCs were shown to preserve tissue and enhance motor function after traumatic brain injury (TBI), 29,33 but its potential therapeutic effect in traumatic SCI has not been explored. On the basis of these considerations, we tested the hypothesis that the enhanced oxygen delivery could minimize the secondary damaging processes and loss of function subsequent to SCI.…”

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confidence: 99%

“…We hypothesize that enhanced oxygen delivery by Oxycyte would preserve tissues and neurons after SCI, because in animal and human studies, PFCs have demonstrated improved outcomes after TBI. 29,33 In addition, we previously studied the effects of Oxycyte on tissue oxygenation post-SCI and demonstrated that perfusion with PFC significantly improved tissue oxygen level in hypoxic tissues. 34 Based primarily on these findings, we tested the hypothesis that the addition of Oxycyte could be beneficial for decreasing ischemic injury and improving functional outcomes after SCI.…”

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confidence: 99%

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Neuroprotective Effects of Perflurocarbon (Oxycyte) after Contusive Spinal Cord Injury

Yacoub

Hajec

Stanger

et al. 2014

Journal of Neurotrauma

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Spinal cord injury (SCI) often results in irreversible and permanent neurological deficits and long-term disability. Vasospasm, hemorrhage, and loss of microvessels create an ischemic environment at the site of contusive or compressive SCI and initiate the secondary injury cascades leading to progressive tissue damage and severely decreased functional outcome. Although the initial mechanical destructive events cannot be reversed, secondary injury damage occurs over several hours to weeks, a time frame during which therapeutic intervention could be achieved. One essential component of secondary injury cascade is the reduction in spinal cord blood flow with resultant decrease in oxygen delivery. Our group has recently shown that administration of fluorocarbon (Oxycyte) significantly increased parenchymal tissue oxygen levels during the usual postinjury hypoxic phase, and fluorocarbon has been shown to be effective in stroke and head injury. In the current study, we assessed the beneficial effects of Oxycyte after a moderate-to-severe contusion SCI was simulated in adult Long-Evans hooded rats. Histopathology and immunohistochemical analysis showed that the administration of 5 mL/kg of Oxycyte perfluorocarbon (60% emulsion) after SCI dramatically reduced destruction of spinal cord anatomy and resulted in a marked decrease of lesion area, less cell death, and greater white matter sparing at 7 and 42 days postinjury. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed a significant reduced number of apoptotic cells in Oxycyte-treated animals, compared to the saline group. Collectively, these results demonstrate the potential neuroprotective effect of Oxycyte treatment after SCI, and its beneficial effects may be, in part, a result of reducing apoptotic cell death and tissue sparing. Further studies to determine the most efficacious Oxycyte dose and its mechanisms of protection are warranted.

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confidence: 99%

mentioning

confidence: 99%

Neuroprotective Effects of Perflurocarbon (Oxycyte) after Contusive Spinal Cord Injury

Yacoub

Hajec

Stanger

et al. 2014

Journal of Neurotrauma

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“…Such models share the ultimate goals of reproducing patterns of tissue damage observed in humans. Our laboratory has extensive experience with two TBI models (Dietrich, Alonso et al 1994;Zhou, Sun et al 2008). In this study we explore the use of those models to assess the relationship between neurodegeneration and immunohistochemical analyses of novel biomarkers.…”

Section: Rodent Models Of Brain Injurymentioning

confidence: 99%

“…Following determination of adequate anesthesia by monitoring toepinch (foot reflex-flexion to pain) and the corneal reflexes, the tail artery is catheterized to aid monitoring of vitals such as blood pressure, blood gases and pH. Detailed descriptions of the procedures have been extensively published (Daugherty, Levasseur et al 2004;Kwon, Sun et al 2005;Zhou, Sun et al 2008). Briefly, the animal is intubated using a shielded 14GA i.v.…”

Section: Acute Subdural Hematoma (Asdh)mentioning

confidence: 99%

Immunohistochemical Correlation of Novel Biomarkers with Neurodegeneration in Rat Models of Brain Injury

Gajavelli¹,

Bregy²,

Spurlock³

et al. 2012

Applications of Immunocytochemistry

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“…Preclinical, and Phase I, II and III clinical trials with PFCOCs have been reported with a Perflubron emulsion (Oxygent™, Alliance Pharmaceutical Corp. San Diego, CA) 7,8 , however this initiative was subsequently abandoned 9,10 . Currently, Oxycyte™ (Synthetic Blood International, Inc. Costa Mesa, CA) remains in clinical trials, has completed Phase II clinical safety trial in Traumatic Brain Injury, and Phase II, dose escalation in Switzerland and Israel [11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Delaying Blood Transfusion in Experimental Acute Anemia With Perfluorocarbon Emulsion

Cabrales¹,

Briceño²

2012

Survey of Anesthesiology

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Background-To avoid unnecessary blood transfusions, physiologic transfusion triggers, rather than exclusively hemoglobin-based transfusion triggers have been suggested. The objective of this study was to determine systemic and microvascular effects of using a perfluorocarbon-based oxygen carrier (PFCOC) to maintaining perfusion and oxygenation during extreme anemia.Methods-The hamster (weight 55-65 g) window chamber model was used. Two isovolemic hemodilution steps were performed using 10% hydroxyethyl starch at normoxic conditions to hematocrit of 19% (5.5 g Hb /dl), point where the transfusion trigger was reached. Two additional hemodilution exchanges using the PFCOC (Oxycyte™, Synthetic Blood International, Inc. Costa Mesa, CA) and increasing fraction of inspired oxygen to 1.0 were performed to reduce hematocrit to 11% (3.8 g Hb /dl) and 6% (2.0 g Hb /dl), respectively. No control group was used in the study, as this level of hemodilution is lethal with conventional plasma expanders. Systemic parameters, microvascular perfusion, functional capillary density and oxygen tensions across the microvascular network were measured.Results-At 6% hematocrit, the PFCOC maintained mean arterial pressure, cardiac output, systemic oxygen delivery and consumption. As hematocrit was lowered from 11% to 6%, functional capillary density, calculated microvascular oxygen delivery and consumption decreased, and oxygen extraction ratio was close to 100%. Peripheral tissue oxygenation was not predicted by systemic oxygenation.Conclusions-PFCOC in conjunction with hyperoxia was able to sustain organ function, and partially provide systemic oxygenation during extreme anemia over the observation period. The PFCOC can work as a bridge until red blood cells are available for transfusion, or where additional oxygen is required, notwithstanding possible limitations in peripheral tissue oxygenation.

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Perfluorocarbon Emulsions Improve Cognitive Recovery After Lateral Fluid Percussion Brain Injury in Rats

Abstract: The current study demonstrates that Oxycyte can improve cognitive recovery and reduce CA3 neuronal cell loss after traumatic brain injury in rats.

Cited by 30 publications

References 52 publications

Neuroprotective Effects of Perflurocarbon (Oxycyte) after Contusive Spinal Cord Injury

Neuroprotective Effects of Perflurocarbon (Oxycyte) after Contusive Spinal Cord Injury

Immunohistochemical Correlation of Novel Biomarkers with Neurodegeneration in Rat Models of Brain Injury

Delaying Blood Transfusion in Experimental Acute Anemia With Perfluorocarbon Emulsion

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