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 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.

Alginate scaffolds improve functional recovery after spinal cord injury.

PURPOSE: In this systematic review and meta-analysis, the use of alginate for the repair of the damaged spinal cord was investigated. METHODS: After an extensive search of databases including MEDLINE, SCOPUS, EMBASE and Web of Science, an initial screening was performed based on inclusion and exclusion criteria. The full text of related articles was reviewed and data mining was performed. Data were analyzed by calculating the mean of ratios between treated and untreated groups using STATA software. Subgroup analysis was also performed due to heterogeneity. Articles were subjected to quality control and PRISMA guidelines were followed. RESULTS: Twelve studies and 17 experiments were included in the study. After SCI, alginate hydrogel had a moderate effect on motor function recovery (SMD = 0.64; 95% CI 0.28-1.00; p < 0.0001) and alginate scaffolds loaded with drugs, growth factors, or cells on the SCI group compared with untreated SCI animals showed has a strong effect in the treatment of SCI (SMD = 2.82; 95% CI 1.49-4.145; p < 0.0001). Treatment with drug/cell in combination with alginate was more strongly significant compared to the groups treated with drug/cell alone (SMD = 4.55; 95% CI 1.42-7.69; p < 0.0001). Alginate alone or in combination therapy when used as an implant, had a more significant effect than injection. CONCLUSION: These findings suggest that alginate is an efficient scaffold for functional recovery and even a much better scaffold for drug/cell delivery after SCI.

Distribution of gold nanoparticles into the brain: a systematic review and meta-analysis.

Despite the widespread use of gold nanoparticles (GNPs), there is no consensus on their distribution to different tissues and organs. The present systematic review and meta-analysis addresses the accumulation of GNPs in brain tissue. Extensive searches were conducted in electronic databases, Medline, Web of Science, EMBASE, and Scopus. Based on inclusion and exclusion criteria, primary and secondary screening was performed. The value of brain accumulation of gold nanoparticle (the percentage of the injection dose of GNPs/gram of brain tissue that applied as effect size (ES) in analysis) and the standard error of the mean were extracted from articles and analyzed by calculating the pooled ES and the pooled confidence interval (CI) using STATA software. p ≤ 0.05 was considered significant. Thirty-eight studies were included in the meta-analysis. The results showed that the amount of GNPs was 0.06% of the injection dose/gram of brain tissue (ES = 0.06, %95 CI: 0.06-0.06, p < 0.0001). Considering the time between injection and tissue harvest (follow-up time), after 1 h the GNPs in brain tissue was 0.288% of the injection dose/gram of tissue (ES = 0.29, 95% CI: 0.25-0.33, p < 0.0001), while after four weeks it was only 0.02% (ES = 0.02, 95% CI: 0.01-0.03, p < 0.0001) of the injection dose/gram of tissue. The amount of GNPs in brain tissue was higher for PEG-coated GNPs compared to uncoated GNPs, and it was 5.6 times higher for rod-shaped GNPs compared to spherical GNPs. The mean amount of GNPs in the brain tissues of animals bearing a tumor was 5.8 times higher than in normal animals.