Abstract
Spinal cord injury (SCI) produces excess reactive oxygen species (ROS) that can exacerbate secondary injury and lead to permanent functional impairment. Hypothesizing that cerium oxide nanoparticles (CONPs) as an effective ROS scavenger may offset this damaging effect, it is first demonstrated in vitro that CONPs suppressed inducible nitric oxide synthase (iNOS) generation and enhanced cell viability of hydrogen peroxide (H2O2)‐insulted cortical neurons. Next, CONPs are administered at various does (50–4000 µg mL−1) to a contused spinal cord rat model and monitored the disease progression for up to eight weeks. At one day postinjury, the number of iNOS+ cells decreases in the treated groups compared with the control. At one week, the cavity size and inflammatory cells are substantially reduced, and the expression of proinflammatory and apoptotic molecules is downregulated with a concurrent upregulation of anti‐inflammatory cytokine. By eight weeks, the treated groups show significantly improved locomotor functions compared with the control. This study shows for the first time that injection of optimal‐dosed CONPs alone into contusion‐injured spinal cord of rats can reduce ROS level, attenuate inflammation and apoptosis, and consequently help locomotor functional recovery, adding a promising and complementary strategy to the other treatments of acute SCI.
Highlights
Introduction easesreduction of reactive oxygen species (ROS) level would be expected to aid the recovery of biological functions of cells in acute injurySpinal cord injury (SCI) is one of the most devastating lesions, conditions
The typical morphology of the cerium oxide nanoparticles (CONPs) was observed by transmission electron microscopy (TEM) (Figure 1a,b)
Cox2 is a peutic drugs, only with nanoparticles “CONPs,” we showed cytokine for the synthesis of prostaglandins and increases right here for the first time the effective role in improving locomotor after SCI,[27] nuclear factor (erythroidderived 2)-like 2 (Nr-f2) modulates inflammation, apoptosis, and regenthe CONPs can be considered a promising candidate for eration,[28] p53 regulates microglia and macrophage proliferacontrolled delivery of anti-inflammatory drugs, to achieve more tion and mitochondrial apoptosis,[29] and caspase 3 (Casp3) is an apoptotic effective and synergistic functions
Summary
The typical morphology of the CONPs was observed by transmission electron microscopy (TEM) (Figure 1a,b). Inset image shows the selected area diffraction pattern, revealing a dotted crystal pattern that is typical of cerium oxide. The hydrodynamic size of the nanoparticles, as measured by a dynamic laser scattering (DLS) assay, showed 33.7 and 127.5 nm in distilled water and neurobasal medium, respectively, suggesting the CONPs are considered to disperse mostly in the form of small clusters (a hundred of nanometers) of single nanoparticles within a cell culture medium (Figure 1c). The Raman spectrum of the nanoparticles reveals the pattern typical of cerium oxide (Figure 1d). The nanoparticles showed a higher incorporation of +4 oxidation status than +3 (with Ce4+/Ce3+ = 2.9), implying that the CONPs possibly consume ROS effectively at the cost of changing their status primarily from Ce4+ to Ce3+.[13]
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