Functional silica nanoparticle-mediated neuronal membrane sealing following traumatic spinal cord injury.
ABSTRACT The mechanical damage to neurons and their processes induced by spinal cord injury (SCI) causes a progressive cascade of pathophysiological events beginning with the derangement of ionic equilibrium and collapse of membrane permeability. This leads to a cumulative deterioration of neurons, axons, and the tissue architecture of the cord. We have previously shown that the application of the hydrophilic polymer polyethylene glycol (PEG) following spinal cord or brain injury can rapidly restore membrane integrity, reduce oxidative stress, restore impaired axonal conductivity, and mediate functional recovery in rats, guinea pigs, and dogs. However there are limits to both the concentration and the molecular weight of the application that do not permit the broadest recovery across an injured animal population. In this study, PEG-decorated silica nanoparticles (PSiNPs) sealed cells, as shown by the significantly reduced leakage of lactate dehydrogenase from damaged cells compared with uncoated particles or PEG alone. Further in vivo tests showed that PSiNPs also significantly reduced the formation of reactive oxygen species and the process of lipid peroxidation of the membrane. Fabrication of PSiNPs containing embedded dyes also revealed targeting of the particles to damaged, but not undamaged, spinal cord tissues. In an in vivo crush/contusion model of guinea pig SCI, every animal but one injected with PSiNPs recovered conduction through the cord lesion, whereas none of the control animals did. These findings suggest that the use of multifunctional nanoparticles may offer a novel treatment approach for spinal cord injury, traumatic brain injury, and possibly neurodegenerative disorders.
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ABSTRACT: The incidence of acute and chronic spinal cord injury (SCI) in the United States is more than 10,000 per year, resulting in 720 cases per million persons enduring permanent disability each year. The economic impact of SCI is estimated to be more than 4 billion dollars annually. Preclinical studies, case reports, and small clinical trials suggest that early treatment may improve neurological recovery. To date, no proven therapeutic modality exists that has demonstrated a positive effect on neurological outcome. Emerging data from recent preclinical and clinical studies offer hope for this devastating condition. This review gives an overview of current basic research and clinical studies for the treatment of SCI.Neurochemical Research 03/2013; · 2.13 Impact Factor
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ABSTRACT: The hydrophilic polymer PEG and its related derivatives, have served as therapeutic agents to reconstruct the phospholipid bilayers of damaged cell membranes by erasing defects in the plasmalemma. The special attributes of hydrophilic polymers when in contact with cell membranes have been used for several decades since these well-known properties have been exploited in the manufacture of monoclonal antibodies. However, while traditional therapeutic efforts to combat traumatic injuries of the central nervous system (CNS) have not been successful, nanotechnology-based drug delivery has become a new emerging strategy with the additional promise of targeted membrane repair. As such, this potential use of nanotechnology provides new avenues for nanomedicine that uses nanoparticles themselves as the therapeutic agent in addition to their other functionalities. Here we will specifically address new advances in experimental treatment of Spinal Cord and Traumatic Brain injury (SCI and TBI respectively). We focus on the concept of repair of the neurolemma and axolemma in the acute stage of injury, with less emphasis on the worthwhile, and voluminous, issues concerning regenerative medicine/nanomedicine. It is not that the two are mutually exclusive - they are not. However, the survival of the neuron and the tissues of white matter are critical to any further success in what will likely be a multi-component therapy for TBI and SCI. This review includes a brief explanation of the characteristics of traumatic spinal cord injury SCI, the biological basis of the injuries, and the treatment opportunities of current polymer-based therapies. In particular, we update our own progress in such applications for CNS injuries with various suggestions and discussion, primarily nanocarrier-based drug delivery systems. The application of nanoparticles as drug-delivery vehicles to the CNS may likely be advantageous over existing molecular-based therapies. As a "proof-of-concept", we will discuss the recent investigations that have preferentially facilitated repair and functional recovery from breaches in neural membranes via rapid sealing and reassembly of the compromised site with silica or chitosan nanoparticles.Experimental Neurology 01/2012; 233(1):126-44. · 4.65 Impact Factor
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ABSTRACT: An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as well as injury current, can be modulated by direct current field stimulation; however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around -70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon illustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cell membrane and the reduction of cation influx.Neural Regeneration Research 09/2013; 8(27):2531-9. · 0.14 Impact Factor