RESUMEN
Neuropathic pain, a debilitating condition, remains a significant challenge due to the lack of effective therapeutic solutions. This study aimed to evaluate the potential of mesenchymal stromal cell (MSC)-derived conditioned medium in alleviating neuropathic pain induced by sciatic nerve compression injury in adult male rats. Forty Wistar rats were randomly assigned to four groups: control, nerve injury, nerve injury with intra-neural injection of conditioned medium, and nerve injury with intra-neural injection of culture medium. Following sciatic nerve compression, the respective groups received either 10 µl of conditioned medium from amniotic fluid-derived stem cells or an equal volume of control culture medium. Behavioral tests for cold allodynia, mechanical allodynia, and thermal hyperalgesia were conducted, and the spinal cord was analyzed using Western Blot and oxidative stress assays. The behavioral experiments showed a decrease in mechanical hyperalgesia and cold allodynia in the group receiving conditioned medium compared to the injury group and the control medium group. Western blot data revealed a decrease in the expression of the CCL2 protein and an increase in GAD65. Oxidative stress tests also showed increased levels of SOD and glutathione in conditioned media-treated animals compared to animals with nerve injury. The findings suggest that conditioned medium derived from amniotic fluid-derived stem cells can effectively reduce neuropathic pain, potentially through the provision of supportive factors that mitigate oxidative stress and inflammation in the spinal cord.
RESUMEN
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.
Asunto(s)
Cerio , Terapia por Luz de Baja Intensidad , Traumatismos de la Médula Espinal , Ratas , Masculino , Animales , Terapia por Luz de Baja Intensidad/efectos adversos , Dolor/complicaciones , Traumatismos de la Médula Espinal/radioterapia , Traumatismos de la Médula Espinal/complicaciones , HiperalgesiaRESUMEN
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.
Asunto(s)
Nanofibras , Nanopartículas , Traumatismos de la Médula Espinal , Ratas , Animales , Masculino , Ratas Wistar , Gelatina , Traumatismos de la Médula Espinal/terapia , Neuronas , Médula Espinal , Regeneración Nerviosa , Andamios del Tejido , MamíferosRESUMEN
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.
Asunto(s)
Curcumina , Traumatismos de la Médula Espinal , Ratas , Ratones , Animales , Curcumina/uso terapéutico , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/tratamiento farmacológico , Modelos Animales de Enfermedad , Recuperación de la Función , Médula Espinal/metabolismoRESUMEN
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.
Asunto(s)
Nanopartículas , Traumatismos de la Médula Espinal , Animales , Cerio , Masculino , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Recuperación de la Función , Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/metabolismoRESUMEN
BACKGROUND: Cell therapy is a promising treatment method for relieving neuropathic pain caused by spinal cord injuries (SCI). Sertoli cells (SCs) are an attractive choice given their demonstrated secretion of growth factors and immunosuppressant effect. This study mechanistically characterizes the analgesic effect of SCs transplantation. METHODS: The clip compression SCI model was carried out on the T12-T13 level in male Wistar rats. One-week post-SCI, SCs were transplanted into the site of injury. Animals underwent Basso, Beattie, and Bresnahan locomotor scoring, mechanical allodynia, and thermal hyperalgesia on a weekly basis for a duration of six weeks. Histological examination of the spinal cord and molecular evaluation of Iba-1, P2Y4, TRPC6, and P-mTOR were performed. SCs survival, measured by anti-Müllerian hormone expression in the spinal cord. RESULTS: Animals that received SCs transplantation showed improvement in motor function recovery and pain relief. Furthermore, a cavity was significantly decreased in the transplanted animals (p = 0.0024), the expression level of TRPC6 and caspase3 and the number of activated microglia decreased compared to the SCI animals, and p-mTOR and P2Y4R expression remarkably increased compared to the SCI group. CONCLUSION: SCs transplantation produces an analgesic effect which may represent a promising treatment for SCI-induced chronic pain.
Asunto(s)
Neuralgia , Traumatismos de la Médula Espinal , Analgésicos , Animales , Trasplante de Células/efectos adversos , Hiperalgesia/etiología , Hiperalgesia/terapia , Masculino , Microglía/metabolismo , Neuralgia/etiología , Neuralgia/metabolismo , Neuralgia/terapia , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Células de Sertoli/metabolismo , Células de Sertoli/patología , Médula Espinal/patología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/terapia , Serina-Treonina Quinasas TOR/metabolismo , Canales Catiónicos TRPC , Canal Catiónico TRPC6/metabolismoRESUMEN
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.
Asunto(s)
Alginatos , Traumatismos de la Médula Espinal , Alginatos/uso terapéutico , Animales , Humanos , Recuperación de la Función , Traumatismos de la Médula Espinal/terapiaRESUMEN
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.
Asunto(s)
Nanopartículas del Metal , Neoplasias , Animales , Encéfalo , Oro , Nanopartículas del Metal/toxicidad , Tamaño de la PartículaRESUMEN
BACKGROUND: Memory deficit is a common cognitive comorbid in patients with neuropathic pain that need better treatment. Recent research revealed that nanocurcumin has an antinociceptive action and a protective effect against memory disorders, suggesting its possible effectiveness for the treatment of neuropathic pain and its comorbidity. METHODS: Adult male albino Wistar rats (n = 32) were randomly divided into four experimental groups: CCI+ nanocurcumin, CCI + vehicle, sham + nanocurcumin, and sham + vehicle. Neuropathic pain induced by a chronic constriction injury of the sciatic nerve. Nanocurcumin or vehicle was injected intraperitoneally for 10 days. Behavioral assessment achieved to evaluate pain threshold in the von Frey test and radiant heat test, also spatial learning and memory examined by the Morris water maze (MWM) test. To explore the possible relation, IL-1ß, and TNF-α levels of the hippocampus measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our data showed that CCI caused neuropathic pain-related behaviors and spatial learning and memory disorders in rats. Chronic treatment with nanocurcumin significantly increased pain threshold (P < 0.001; F = 27.63, F = 20.58), improved spatial memory (P < 0.01; F = 47.37), and decreased the hippocampal levels of IL-1ß (P < 0.001; F = 33.57) and TNF-α (P < 0.01; F = 7.25) in CCI rats. CONCLUSION: Chronic nanocurcumin can ameliorate pain-related behavior, improve spatial learning and memory deficits, and is associated with the reduction of IL-1ß and TNF-α levels in the hippocampus in CCI rats. Nanocurcumin may be potentially providing a therapeutic alternative for the treatment of neuropathic pain and its memory impairment comorbidity.
Asunto(s)
Analgésicos/uso terapéutico , Curcumina/uso terapéutico , Hipocampo/efectos de los fármacos , Interleucina-1beta/metabolismo , Neuralgia/tratamiento farmacológico , Memoria Espacial/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Analgésicos/administración & dosificación , Analgésicos/química , Animales , Conducta Animal/efectos de los fármacos , Constricción , Curcumina/administración & dosificación , Curcumina/química , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Masculino , Trastornos de la Memoria/complicaciones , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Nanopartículas/administración & dosificación , Nanopartículas/química , Neuralgia/complicaciones , Neuralgia/metabolismo , Umbral del Dolor/efectos de los fármacos , Ratas , Ratas Wistar , Nervio Ciático/efectos de los fármacos , Nervio Ciático/lesionesRESUMEN
BACKGROUND: Neuropathic pain following injury or dysfunction of the peripheral or CNS is one of the most important medical challenges to treat. Humane platelet-rich plasma (HPRP), which is a rich source of growth factors, may be able to treat and reduce pain caused by spinal cord injury (SCI). In this study, the effect of HPRP on neuropathic pain caused by SCI was investigated. METHODS: Sixty adult male Wistar rats were randomly divided into 6 groups: control, sham, SCI, vehicle (SCI+platelet-poor plasma), SCI+ PRP2day (injection 48 hrs after SCI) and SCI+PRP14day (injection 14 days after SCI). SCI was induced at the T12-T13 level. Behavioral tests were conducted weekly after injury for six weeks. Allodynia and hyperalgesia were assessed using acetone drops, plantar test and von Frey filament. Cavity size and the number of fibroblasts were determined by H&E stain, and the expression of mTOR, p-mTOR, P2×3R and P2Y4R were determined using the western blot technique. Data were analyzed using PRISM & SPSS software. RESULTS: PRP injection showed a higher pain threshold in mechanical allodynia (p<0.0001), cold allodynia (p<0.0001) and thermal hyperalgesia (p<0.0001) than those in the spinal. Animals treated with PRP also reduced cavity size, fibroblast number, p-mTOR/mTOR ratio, and P2×3R expression, and increased P2Y4R expression. The difference between the two groups was not statistically significant. CONCLUSIONS: The results showed that PRP reduced SCI-induced allodynia and hyperalgesia by regulating ATP signaling. Using HPRP can open a new window in the treatment of pain caused by damage to the nervous system.