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Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats.

ABSTRACT: Since the CNS is unable to repair itself via neuronal regeneration in adult mammals, alternative therapies need to be found. The use of cerium oxide nanoparticles to repair nerve damage could be a promising approach for spinal cord reconstruction. In this study, we constructed a scaffold containing cerium oxide nanoparticles (Scaffold-CeO₂) and investigated the rate of nerve cell regeneration in a rat model of spinal cord injury. The scaffold of gelatin and polycaprolactone was synthesized, and a gelatin solution containing cerium oxide nanoparticles was attached to the scaffold. For the animal study, 40 male Wistar rats were randomly divided into 4 groups (n = 10): (a) Control; (b) Spinal cord injury (SCI); (c) Scaffold (SCI + scaffold without CeO₂ nanoparticles); (d) Scaffold-CeO₂ (SCI + scaffold containing CeO₂ nanoparticles). After creation of a hemisection SCI, scaffolds were placed at the site of injury in groups c and d, and after 7 weeks the rats were subjected to behavioral tests and then sacrificed for preparation of the spinal cord tissue to measure the expression of G-CSF, Tau and Mag proteins by Western blotting and Iba-1 protein by immunohistochemistry. The result of behavioral tests confirmed motor improvement and pain reduction in the Scaffold-CeO₂ group compared to the SCI group. Decreased expression of Iba-1 and higher expression of Tau and Mag in the Scaffold-CeO₂ group compared to the SCI group could be the result of nerve regeneration caused by the scaffold containing CeONPs as well as relief of pain symptoms.

SUBMITTER: Rahimi B

PROVIDER: S-EPMC9944598 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats.

Rahimi Behnaz B Behroozi Zahra Z Motamednezhad Ali A Jafarpour Maral M Hamblin Michael R MR Moshiri Ali A Janzadeh Atousa A Ramezani Fatemeh F

Journal of materials science. Materials in medicine 20230221 2

Since the CNS is unable to repair itself via neuronal regeneration in adult mammals, alternative therapies need to be found. The use of cerium oxide nanoparticles to repair nerve damage could be a promising approach for spinal cord reconstruction. In this study, we constructed a scaffold containing cerium oxide nanoparticles (Scaffold-CeO<sub>2</sub>) and investigated the rate of nerve cell regeneration in a rat model of spinal cord injury. The scaffold of gelatin and polycaprolactone was synthe ...[more]

PMID: 36809518

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Project description:BackgroundSpinal cord injury (SCI) treatment remains a formidable challenge, as current therapeutic approaches provide only marginal relief and fail to reverse the underlying tissue damage. This study aims to develop a novel composite material combining enzymatic nanoparticles and nerve growth factor (NGF) to modulate the immune microenvironment and enhance SCI repair.MethodsCeMn nanoparticles (NP) and CeMn NP-polyethylene glycol (PEG) nanozymes were synthesized via sol-gel reaction and DSPE-mPEG modification. Transmission Electron Microscopy, Selected-Area Electron Diffraction, X-ray Diffraction and X-ray Photoelectron Spectroscopy confirmed their crystalline structure, mixed-valence states, and redox properties. Size uniformity, biocompatibility, and catalytic activity were assessed via hydrodynamic diameter, zeta potential, and elemental analysis. The Lightgel/NGF/CeMn NP-PEG composite was synthesized and characterized via electron microscopy, compression testing, rheological analysis, NGF release kinetics, and 30-day degradation studies. Both in vitro and in vivo experiments were conducted to evaluate the therapeutic effects of the composite on SCI.ResultsThe Lightgel/NGF/CeMn NP-PEG composite was successfully synthesized, exhibiting favorable physical properties. At a CeMn NP-PEG concentration of 4 µg/mL, the composite maintained cell viability and demonstrated enhanced biological activity. It also showed superior mechanical properties and an effective NGF release profile. Notably, the composite significantly upregulated the expression of nerve growth-associated proteins, reduced inflammatory cytokines, scavenged reactive oxygen species (ROS), and promoted M2 macrophage polarization by inhibiting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. In a rat SCI model, it facilitated functional recovery and attenuated inflammation.ConclusionThe Lightgel/NGF/CeMn NP-PEG composite shows significant therapeutic promise for SCI, effectively eliminating ROS, promoting M2 macrophage polarization, reducing pro-inflammatory cytokines, and supporting neuronal regeneration. These effects substantially enhance motor function in SCI rats, positioning it as a promising candidate for future clinical applications.

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Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats.

Publications

Study of nerve cell regeneration on nanofibers containing cerium oxide nanoparticles in a spinal cord injury model in rats.

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