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

Abstract

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.

Oxygen Sensing with Perfluorocarbon-Loaded Ultraporous Mesostructured Silica Nanoparticles

“…PFCs used for oxygen sensing or delivery have been established in the literature, including: perfluoro-15-crown-5-ether (PFCE), hexafluorobenzene (HFB), perfluorodecalin (PFD), perfluorooctyl bromide (PFOB), perfluoro(tert-butylcyclohexane) (PFTBCH), and perfluorotributylamine (PFTBA). 27–32 …”

Brain oxygenation with a non‐vasoactive perfluorocarbon emulsion in a rat model of traumatic brain injury

“…Treatment with Oxycyte has been shown to improve outcome following pathophysiological conditions other than TBI where damage to the vasculature and/or alterations in microvascular function occur and result in hypoxic injury. Specifically, in a model of spinal cord contusion, Oxycyte was shown to increase tissue oxygenation, to have neuroprotective properties, and to reduce apoptotic cell death . In addition, Oxycyte may also be a promising treatment for decompression sickness, which is believed to be associated with the formation of gas bubbles during depressurization that lead to arterial embolization with various symptoms including, neurological manifestations and spinal cord injury .…”

Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury

“…Yacoub et al used Oxycyte, an intravenous injectable perfluorocarbon, to relieve the long-lasting ischemia and hypoxia resulting post-SCI by improving the tissue oxygenation in a contusion model, and reported decreased lesion sizes with improved locomotor function and white matter preservation (52). Although they focused on the use of Oxycyte as a monotherapy, the authors proposed a combinative therapy with other immunomodulatory compounds that are already FDA approved, such as FTY 720 (27).…”