Abstract
BackgroundTraumatic spinal cord injury (SCI) leads to serious neurological and functional deficits through a chain of pathophysiological events. At the molecular level, progressive damage is initially revealed by collapse of plasma membrane organization and integrity produced by breaches. Consequently, the loss of its role as a semi-permeable barrier that generally mediates the regulation and transport of ions and molecules eventually results in cell death. In previous studies, we have demonstrated the functional recovery of compromised plasma membranes can be induced by the application of the hydrophilic polymer polyethylene glycol (PEG) after both spinal and brain trauma in adult rats and guinea pigs. Additionally, efforts have been directed towards a nanoparticle-based PEG application.The in vivo and ex vivo applications of PEG-decorated silica nanoparticles following CNS injury were able to effectively and efficiently enhance resealing of damaged cell membranes.ResultsThe possibility for selectivity of tetramethyl rhodamine-dextran (TMR) dye-doped, PEG-functionalized silica nanoparticles (TMR-PSiNPs) to damaged spinal cord was evaluated using an ex vivo model of guinea pig SCI. Crushed and nearby undamaged spinal cord tissues exhibited an obvious difference in both the imbibement and accumulation of the TMR-PSiNPs, revealing selective labeling of compression-injured tissues.ConclusionsThese data show that appropriately functionalized nanoparticles can be an efficient means to both 1.) carry drugs, and 2.) apply membrane repair agents where they are needed in focally damaged nervous tissue.
Highlights
Traumatic spinal cord injury (SCI) leads to serious neurological and functional deficits through a chain of pathophysiological events
Others have experimented with the addition of Magnesium salts to the polyethylene glycol (PEG) solution in SCI [25] and found benefit in different types of adult rat SCI behavioral models [26,27]
The suitable functionalization of the nanoparticles enables a possible preferential recognition of specific cells, facilitating binding and affinity-based endocytosis. Inspired by these important features, silica nanoparticles were functionalized with recognition elements, or PEG, on their surfaces, expecting localization toward injured tissue (Figure 2)
Summary
Traumatic spinal cord injury (SCI) leads to serious neurological and functional deficits through a chain of pathophysiological events. We have demonstrated the functional recovery of compromised plasma membranes can be induced by the application of the hydrophilic polymer polyethylene glycol (PEG) after both spinal and brain trauma in adult rats and guinea pigs. From a practical standpoint, such limitations would not allow for sufficient flexibility in preparation and application of PEG, and might restrict the appropriate use of systemic/ intravenous polymers for maximum efficacy and efficiency To overcome these problems, we have shifted our research focus toward the development of nanoparticle-based membrane applications systems. While the systemic footprint of the polymer would likely be undetectable [37], ii) PEG-conjugated particles diminish the current challenges that could arise from the solution-based administration Such nanocarrier systems minimize the amount of free drug in solution, and prevent polymer degradation and inactivation upon administration, [36,38] and iii) the small size of nanoparticles affords their internalization inside cells while evading uptake by phagocytic cells [39]. Acrolein is a potent natural aldehyde toxin created as an endpoint to LPO following mechanical trauma to cells [42]
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