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.

Cost-effectiveness of remdesivir for the treatment of hospitalized patients with COVID-19: a systematic review.

BACKGROUND: Remdesivir is being studied and used to treat coronavirus disease 2019 (COVID-19). This study aimed to systematically identify, critically evaluate, and summarize the findings of the studies on the cost-effectiveness of remdesivir in the treatment of hospitalized patients with COVID-19. METHODS: In this systematic review, PubMed, EMBASE, Web of Science, SCOPUS, and the Cochrane Library were searched for studies published between 2019 and 2022. We included all full economic evaluations of remdesivir for the treatment of hospitalized patients with COVID-19. Data were summarized in a structured and narrative manner. RESULTS: Out of 616 articles obtained in this literature search, 12 studies were included in the final analysis. The mean score of the Quality of Health Economic Studies (QHES) for the studies was 87.66 (high quality). All studies were conducted in high-income countries (eight studies in the USA and one study in England), except for three studies from middle-to-high-income countries (China, South Africa, and Turkey). Six studies conducted their economic analysis in terms of a health system perspective; five studies conducted their economic analysis from a payer perspective; three studies from the perspective of a health care provider. The results of five studies showed that remdesivir was cost-effective compared to standard treatment. Furthermore, the therapeutic strategy of combining remdesivir with baricitinib was cost-effective compared to remdesivir alone. CONCLUSIONS: Based on the results of the present study, remdesivir appears to be cost-effective in comparison with the standard of care in China, Turkey, and South Africa. Studies conducted in the United States show conflicting results, and combining remdesivir with baricitinib is cost-effective compared with remdesivir alone. However, the cost-effectiveness of remdesivir in low-income countries remains unknown. Thus, more studies in different countries are required to determine the cost-effectiveness of this drug.

The effect of gabapentin and pregabalin administration on memory in clinical and preclinical studies: a meta-analysis and systematic review.

BACKGROUND: Today, gabapentinoids such as Gabapentin (GBP) and pregabalin (PGB) are widely used as painkillers. This may alter the function of the nervous system; hence their results may include a difference in memory and processes that end in memory formation. This study aims to conclude whether gabapentinoids can alter memory or not by reviewing and analyzing clinical and preclinical studies. MATERIAL AND METHODS: A comprehensive search was carried out in databases including PUBMED, EMBASE, SCOPUS, and Web of Science. In the included studies, memory was measured as an outcome variable in clinical or preclinical studies. RESULT: A total of 21 articles (4 clinical, 17 preclinical) were included in the meta-analysis by STATA Software. The results showed that memory changes under the influence of GBP. Both the administrated dosage and the time of administration are important in the final results and latency time of retention. GBP administration in healthy animals increased latency time, whereas if the administration of GBP took place exactly before training, the latency time increased slightly. Short-term administration of PGB in healthy volunteers is accompanied by transient side effects on the CNS. However, the number and homogeneity of the studies were not such that a meta-analysis could be performed on them. CONCLUSION: Clinical and preclinical studies showed that PGB administration did not confirm its improving memory effect. GBP administration in healthy animals increased latency time and improved memory. Although it depended on the time of administration.

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.

Neurotoxicity of silver nanoparticles in the animal brain: a systematic review and meta-analysis.

OBJECTIVE: About 30% of all nanoparticle products contain silver nanoparticles (AgNPs). With the increasing use of AgNPs in industry and medicine, concerns about the adverse effects on the environment, and the possible toxicity of these particles to primary cells and towards organs such as the brain and nervous system increased. In this paper, the toxicity of AgNPs in neurons and brain of animal models was investigated by a systematic review and meta-analysis. METHODS: The full texts of 26 relevant studies were reviewed and analyzed. Data from nine separate experiments in five articles were analyzed by calculating the standardized mean differences between viability of treated animals and untreated groups. Subgroup analysis was conducted. In addition, a systematic review provided a complete, exhaustive summary of all articles. RESULTS: The results of the meta-analysis showed that AgNPs are able to cause neuronal death after entering the brain (standardized mean difference (SMD) = 2.87; 95% confidence interval (CI) 2.1-3.61; p < 0.001). AgNPs sized smaller or larger than 10 nm could both cause neuronal cell death. This effect could be observed for a long time (up to 6 months). Neurons from embryonic animals whose mothers had been exposed to AgNPs during pregnancy were affected as much as animals that were themselves exposed to AgNPs. Toxic effects of AgNPs on memory and cognitive function were also observed. Studies have shown that inflammation and increased oxidative stress followed by apoptosis are likely to be the main mechanisms of AgNPs toxicity. CONCLUSION: AgNPs can enter the brain with a long half-life and it can cause neuronal death after entering the brain. AgNPs can manifest proinflammatory cascades in the CNS and BBB. Some toxic effects were detected in the cerebral cortex, hypothalamus, hippocampus and others. Studies have shown that inflammation and increased oxidative stress lead to apoptosis, the main mechanism of AgNPs neurotoxicity, which can be caused by an increase in silver ions from AgNPs.

Sustained delivery of chABC improves functional recovery after a spine injury.

INTRODUCTION: Chondroitinase ABC (chABC) is an enzyme could improve regeneration and thereby improving functional recovery of spinal cord injury (SCI) in rodent models. Degradation of the active enzyme and diffusion away from the lesion are the causes of using hydrogels as a scaffold to deliver the chABC into the lesion site. In this meta-analysis, we investigated the effects of chABC embedded in a scaffold or hydrogel on the functional recovery after SCI. METHOD: Databases were searched based on keywords related to chABC and spinal cord injury (SCI). Primary and secondary screening was performed to narrow down study objectives and inclusion criteria, and finally the data were included in the meta-analysis. The standard mean difference of the score of the functional recovery that measured by Basso, Beattie, Bresnahan (BBB) test after SCI was used to analyze the results of the reported studies. Subgroup analysis was performed based on SCI model, severity of SCI, transplantation type, and the follow-up time. Quality control of articles was also specified. RESULTS: The results showed that embedding chABC within the scaffold increased significantly the efficiency of functional recovery after SCI in animal models (SMD = 1.95; 95% CI 0.71-3.2; p = 0.002) in 9 studies. SCI model, severity of SCI, injury location, transplantation type, and the follow-up time did not affect the overall results and in all cases scaffold effect could not be ignored. However, due to the small number of studies, this result is not conclusive and more studies are needed. CONCLUSION: The results could pave the way for the use of chABC embedded in the scaffold for the treatment of SCI and show that this method of administration is superior to chABC injection alone.

Human umbilical cord blood-derived platelet -rich plasma: a new window for motor function recovery and axonal regeneration after spinal cord injury.

BACKGROUND: There are complex mechanisms for reducing intrinsic repairability and neuronal regeneration following spinal cord injury (SCI). Platelet-rich plasma (PRP) is a rich source of growth factors and has been used to motivate the regeneration of peripheral nerves in neurodegenerative disorders. However, only a few studies have shown the effects of PRP on the SCI models. METHODS: We investigated whether PRP derived from human umbilical cord blood (HUCB-PRP) could recover motor function in animals with spinal cord injury. Sixty adult male Wistar rats were randomly divided into 6 groups (n=60) as control, sham (laminectomy without induction of spinal cord injury), SCI, vehicle (SCI+ Platelet-Poor Plasma), PRP2day (SCI+PRP injection 2 days after SCI), and PRP14day (SCI+PRP injection 14 days after SCI). SCI was performed at the T12-T13 level. BBB test was carried out weekly after injury for six weeks. Caspase3 expression was determined using the Immunohistochemistry technique. The expression of GSK3ß, CSF-tau, and MAG was determined using the Western blot technique. Data were analyzed by PRISM & SPSS software. RESULTS: HUCB-PRP treated animals showed a higher locomotor function recovery than those in the SCI group (p<0.0001). The level of caspase3, GSK3ß and CSF- Tau reduced and the MAG level in the spinal cord increased by the injection of HUCB-PRP in SCI animals. CONCLUSION: Injection of HUCB-PRP enhanced hind limb locomotor performance by modulation of caspase3, GSK3ß, CSF-tau, and MAG expression. Using HUCB-PRP could be a new therapeutic option for recovering motor function and axonal regeneration after SCI.

Injection of Cerium Oxide Nanoparticles to Treat Spinal Cord Injury in Rats.

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.

Sertoli cell transplantation attenuates microglial activation and inhibits TRPC6 expression in neuropathic pain induced by spinal cord injury.

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.

Pain Alleviating Effect of Adipose-Derived Stem Cells Transplantation on the Injured Spinal Cord: A Behavioral and Electrophysiological Evaluation.

Few studies are conducted on the efficacy of human adipose-derived stem cells (ADSCs) in spinal cord injury (SCI) management and electrophysiological changes in the spinal cord. Therefore, the present study aimed to determine the effect of ADSCs on neuropathic pain, motor function recovery, and electrophysiology assessment. For the purpose of this study, adult male Wistar rats (weight: 140-160 gr, n = 42) were randomly allocated into five groups namely intact animals, sham-operated, SCI non-treated animals, vehicle-treated (culture media), and ADSCs treated groups. One week after clips compression SCI induction, about 1×106 cells were transplanted into the spinal cord. As well, both neuropathic pain (allodynia and hyperalgesia) and motor function were measured weekly. Cavity size, ADSCs survival, and electrophysiology assessments were measured at the end of the eighth week. The transplantation of ADSCs resulted in a significant improvement in the locomotion of SCI animals (p<0.0001), mechanical allodynia (p<0.0001), cold allodynia (p<0.0001), mechanical hyperalgesia (p<0.0001), and thermal hyperalgesia (p<0.0001). The cavity size was significantly smaller among the ADSCs-treated animals (p <0.0001). The single-unit recording showed that the transplantation of ADSCs decreased wide dynamic range (WDR) in neurons and it evoked potential in response to receiving signals from Aß (p<0.0001) and Aδ (p=0.003) C-fiber (p<0.0001) neurons. Post-discharge recorded from WDR neurons decreased after the transplantation of ADSCs (p<0.0001) and wind up in the ADSCs-treated group was lower than that of the SCI group (p=0.003). Our results showed that the transplantation of ADSCs could significantly alleviate neuropathic pain, enhance motor function recovery, and improve electrophysiology findings after SCI.

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.

Prevalence of depression, anxiety, and psychological distress in patients with epilepsy during COVID-19: A systematic review.

OBJECTIVE: COVID-19 pandemic disease has profound consequences for physical and mental health. In this regard, health care for chronic diseases, especially epilepsy is neglected The purpose of this systematic review study was to investigate the epidemic effect of COVID-19 on increasing the prevalence of mental disorders such as depression, anxiety, and sleep disorders in people with epilepsy (PWE). METHODS: We systematically searched MEDLINE, Cochrane, Embase, Web of science, Scopus, and Psych info databases for studies that estimate the prevalence of mental disorders in PWE during the COVID-19 until December 2020. Inclusion criteria included samples of population, with a confirmed diagnosis of epilepsy. RESULTS: Irrespective of PWE or people without epilepsy (PWOE), all experienced stress and anxiety during COVID-19 pandemic. Most of the studies showed that PWE and even PWOE during the pandemic, suffer from depression. The highest rate of depression was attributed to female PWE with financial problems (66.7%) and the lowest rate of depression in PWE was reported in 8.6%. 7.1-71.2% and 28.2% of patients reported sleep disorders and insomnia, respectively. Less than 2% experienced a sleep improvement. LIMITATIONS: Due to a large amount of heterogeneities across the results, we could not evaluate the exact rate of prevalence in spite of using effective measures. CONCLUSIONS: People with epilepsy were considered as a susceptible group to the impact of the pandemic. Therefore, great attention should be paid to PWE and adequate psychological supports provided in this period to relieve or inhibit risks to mental health in PWE.

The Value of Physiological Scoring Criteria in Predicting the In-Hospital Mortality of Acute Patients; a Systematic Review and Meta-Analysis.

INTRODUCTION: There is no comprehensive meta-analysis on the value of physiological scoring systems in predicting the mortality of critically ill patients. Therefore, the present study intended to conduct a systematic review and meta-analysis to collect the available clinical evidence on the value of physiological scoring systems in predicting the in-hospital mortality of acute patients. METHOD: An extensive search was performed on Medline, Embase, Scopus, and Web of Science databases until the end of year 2020. Physiological models included Rapid Acute Physiology Score (RAPS), Rapid Emergency Medicine Score (REMS), modified REMS (mREMS), and Worthing Physiological Score (WPS). Finally, the data were summarized and the findings were presented as summary receiver operating characteristics (SROC), sensitivity, specificity and diagnostic odds ratio (DOR). RESULTS: Data from 25 articles were included. The overall analysis showed that the area under the SROC curve of REMS, RAPS, mREMS, and WPS criteria were 0.83 (95% CI: 0.79-0.86), 0.89 (95% CI: 0.86-0.92), 0.64 (95% CI: 0.60-0.68) and 0.86 (95% CI: 0.83-0.89), respectively. DOR for REMS, RAPS, mREMS and WPS models were 11 (95% CI: 8-16), 13 (95% CI: 4-41), 2 (95% CI: 2-4) and 17 (95% CI: 5-59) respectively. When analyses were limited to trauma patients, the DOR of the REMS and RAPS models were 112 and 431, respectively. Due to the lack of sufficient studies, it was not possible to limit the analyses for mREMS and WPS. CONCLUSION: The findings of the present study showed that three models of RAPS, REMS and WPS have a high predictive value for in-hospital mortality. In addition, the value of these models in trauma patients is much higher than other patient settings.

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.

Platelet-rich plasma in umbilical cord blood reduces neuropathic pain in spinal cord injury by altering the expression of ATP receptors.

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.