Combined effect of Cerium oxide nanoparticles loaded scaffold and photobiomodulation therapy on pain and neuronal regeneration following spinal cord injury: an experimental study.

BACKGROUND: Spinal cord injury (SCI) remained one of the challenges to treat due to its complicated mechanisms. Photobiomodulation therapy (PBMT) accelerates neuronal regeneration. Cerium oxide nanoparticles (CeONPs) also eliminate free radicals in the environment. The present study aims to introduce a combined treatment method of making PCL scaffolds as microenvironments, seeded with CeONPs and the PBMT technique for SCI treatment. METHODS: The surgical hemi-section was used to induce SCI. Immediately after the SCI induction, the scaffold (Sc) was loaded with CeONPs implanted. PBMT began 30 min after SCI induction and lasted for up to 4 weeks. Fifty-six male rats were randomly divided into seven groups. Glial fibrillary acidic protein (GFAP) (an astrocyte marker), Connexin 43 (Con43) (a member of the gap junction), and gap junctions (GJ) (a marker for the transfer of ions and small molecules) expressions were evaluated. The behavioral evaluation was performed by BBB, Acetone, Von Frey, and radiant heat tests. RESULT: The SC + Nano + PBMT group exhibited the most remarkable recovery outcomes. Thermal hyperalgesia responses were mitigated, with the combined approach displaying the most effective relief. Mechanical allodynia and cold allodynia responses were also attenuated by treatments, demonstrating potential pain management benefits. CONCLUSION: These findings highlight the potential of PBMT, combined with CeONPs-loaded scaffolds, in promoting functional motor recovery and alleviating pain-related responses following SCI. The study underscores the intricate interplay between various interventions and their cumulative effects, informing future research directions for enhancing neural repair and pain management strategies in SCI contexts.

Evaluation of epigenetic (HDAC, DNMT) and pain (Gad65, TGF) factors following photobiomodulation therapy in a neuropathic pain model.

Photobiomodulation therapy (PBMT) is converted to the most common analgesic treatment before the whole mechanism is yet to be discovered. This study for the first time was designed to investigate alternations of epigenetic factors after pain and PBMT. The CCI model was chosen to induce pain. Pain evaluation tests including plantar, acetone, von Frey, and pinch were done weekly. Then spinal cord tissue was isolated for evaluating mRNA expression of DNMT3a, HDAC1, and NRSF using RT-qPCR method, and protein expression factors of HDAC2 and DNMT3a using western blotting. GAD65 and TGF-ß proteins were assessed by the IHC method. PBMT increased the pain threshold up to the point where it roughly met the pain threshold of the control group. After three weeks of treatment, both PBMT protocols demonstrated a reduction in allodynia and hyperalgesia. While some molecules, such as TGF-ß and Gad65, increased following PBMT, we observed no inhibition of NRSF, HDAC1, and DNMT3a expression despite implementing two different protocols.

Evaluation of photobiomodulation therapy (117 and 90s) on pain, regeneration, and epigenetic factors (HDAC 2, DNMT3a) expression following spinal cord injury in a rat model.

BACKGROUND: Photobiomodulation therapy (PBMT), due to its anti-inflammatory, analgesic effects, and most importantly as a non-invasive procedure, has currently gained a special setting in pain relief and the treatment of Spinal cord injuries (SCI). However, the mechanism of action of the PBM is not yet completely understood. METHODS: In this study, SCI is induced by an aneurysm clip, and PBM therapy was applied by a continuous-wave (CW) laser with a wavelength of 660 nm. Adult male rats were divided into four groups: Control, SCI, SCI + PBMT 90s, and SCI + PBMT 117s. After 7 weeks, hyperalgesia, allodynia, and functional recovery were assessed. Fibroblasts infiltrating the spinal cord were counted after H&E staining. The expression of epigenetic factors (HDAC2, DNMT3a), protein relevant for pain (GAD65), and astrocytes marker (GFAP) after 4 weeks of daily PBMT (90 and 117s) was probed by western blotting. RESULTS: Both PBMTs (90 and 117s) significantly improved the pain and ability to move and fibroblast invasion was reduced. SCI + PBMT 90s, increased GAD65, HDAC2, and DNMT3a expression. However, PBMT 117s decreased GFAP, HDAC2, and DNMT3a. CONCLUSION: PBMT 90 and 117s improved the pain, and functional recovery equally. The regulation of epigenetic mechanisms appears to be a significant effect of PBMT117s, which emphasizes on impact of radiation duration and accumulative energy.

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

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.

The potential of curcumin for treating spinal cord injury: a meta-analysis study.

INTRODUCTION: In this paper, we conducted a meta-analysis on the curcumin effect on functional recovery provided by the Basso, Beattie, Brenham (BBB) test for rats, and the Basso mouse scale (BMS) for mice after spinal cord injury (SCI) in animal models. METHOD: Data mining was performed, and the standard mean difference (SMD) between the treated and control (untreated) groups was calculated using the STATA software. Quality control and subgroup analysis were performed. RESULTS: The analysis includes 24 experimental studies that showed curcumin had a strong significance in improving functional recovery after SCI (SMD = 3.38; 95% CI: 2.54-4.22; p < 0.001). When curcumin was administered daily, it had a stronger effect than single-dose treatment or weekly administration. Despite the same effect in the follow-up time before and after 4 weeks post-injury, but later 9 weeks, curcumin had only a moderate effect. Curcumin also significantly reduced the expression of GFAP (Glial fibrillary acidic protein) marker compared to untreated groups. CONCLUSION: These findings suggest that daily administration of curcumin can be an effective approach to improving functional recovery after SCI.