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This study investigated the effects of local injection of cerium oxide nanoparticles (CeONPs) in a rat spinal cord injury (SCI) model. Thirty-six adult male Wistar rats were divided into 4 groups: controls (healthy animals), sham (laminectomy), SCI (laminectomy+SCI induction), and treatment (laminectomy+SCI induction+intrathecal injection of CeONPs immediately after injury). SCI was induced using an aneurysm clip at the T12-T13 vertebral region. Motor performance and pain threshold tests were performed weekly; H&E staining and measurement of cavity sizes were performed 6 weeks after injury. The expression of granulocyte colony-stimulating factor (GCSF), P44/42 MAPK, P-P44/42 MAPK, Tau, myelin-associated glycoprotein(MAG) was evaluated after 6 weeks by Western blot. The Basso, Beattie, and Bresnahan locomotor scoring scales improved in animals receiving CeONPs compared with SCI animals. The cavity sizes were less in the treatment group. GCSF expression was similar in the animals receiving CeONPs compared with the SCI group but the expression of ERK1/ERK2 and phospho-ERK was lower than in the SCI group. Expression levels of Tau and MAG were significantly increased in treated animals compared to the SCI group. These data indicate that the use of CeONPs may improve motor functional recovery in SCI.

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Introduction: The present study, investigated the local injection of cerium oxide nanoparticles (CeONPs) into Spinal cord injury (SCI) lesions in rats, and the effect on motor performance and neuropathic pain, together with biochemical markers.Methods: 36 adult male Wistar rats were divided into 4 groups: control group (healthy animals); sham group (laminectomy); SCI group (laminectomy+SCI induction); treatment group (laminectomy + SCI induction + intrathecal injection of 10 µL of CeONPs (1000 µg/mL) immediately after injury). SCI was induced by application of an aneurysm clip at the T12-T13 vertebral region. Immediately after SCI, CeONPs were injected into the treatment group with a Hamilton syringe and micropipet. H&E staining and measurement of the size of the cavity were performed after 6 weeks, and the BBB motor performance test and pain threshold test were performed weekly. GCSF expression, P44/42 MAPK (ERK1/ERK2), P-P44/42 MAPK (ERK1/ERK2), total Tau, total MAG, β-actin were evaluated after 6 weeks.Results: The BBB score and pain threshold improved in animals receiving CeONPs compared with SCI animals. The size of the cavity decreased in the treatment group. GCSF protein expression levels were similar in animals receiving CeONPs compared with the SCI group, but the expression of ERK1/ERK2 and phospho-ERK was lower compared with the SCI group. The expression levels of Tau and MAG were significantly increased in treated animals compared to the SCI group.Conclusion: The use of CeONPs in SCI could improve motor functional recovery, reduce pain and increase nerve cell regeneration.

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. Graphical Abstract

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