Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model.
Ontology highlight
ABSTRACT:
SUBMITTER: Kim SJ
PROVIDER: S-EPMC8398565 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Compression spinal cord injuries are a common cause of morbidity in people who experience a spinal cord injury (SCI). Either as a by-product of a traumatic injury or due to nontraumatic conditions such as cervical myelitis, compression injuries are growing in prevalence clinically and many attempts of animal replication have been described within the literature. These models, however, often focus on the traumatic side of injury or mimic short-term injuries that are not representative of the majority of compression SCI. Of this, nontraumatic spinal cord injuries are severely understudied and have an increased prevalence in elderly populations, adults, and children. Therefore, there is a need to critically evaluate the current animal models of compression SCI and their suitability as a method for clinically relevant data that can help reduce morbidity and mortality of SCI. In this review, we reviewed the established and emerging methods of animal models of compression SCI. These models are the clip, balloon, solid spacer, expanding polymer, remote, weight drop, calibrated forceps, screw, and strap methods. These methods showed that there is a large reliance on the use of laminectomy to induce injury. Furthermore, the age range of many studies does not reflect the elderly and young populations that commonly suffer from compression injuries. It is therefore important to have techniques and methods that are able to minimize secondary effects of the surgeries, and are representative of the clinical cases seen so that treatments and interventions can be developed that are specific.
| S-EPMC9825893 | biostudies-literature
Project description:Study designSystematic review.ObjectiveSpinal cord injuries (SCIs) resulting in motor deficits can be devastating injuries resulting in millions of health care dollars spent per incident. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a potential class of drugs that could improve motor function after an SCI. This systematic review utilizes PRISMA guidelines to evaluate the effectiveness of NSAIDs for SCI.MethodsPubMed/MEDLINE, CINAHL, PsycINFO, Embase, and Scopus were reviewed linking the keywords of "ibuprofen," "meloxicam," "naproxen," "ketorolac," "indomethacin," "celecoxib," "ATB-346," "NSAID," and "nonsteroidal anti-inflammatory drug" with "spinal." Results were reviewed for relevance and included if they met inclusion criteria. The SYRCLE checklist was used to assess sources of bias.ResultsA total of 2960 studies were identified in the PubMed/MEDLINE database using the above-mentioned search criteria. A total of 461 abstracts were reviewed in Scopus, 340 in CINAHL, 179 in PsycINFO, and 7632 in Embase. A total of 15 articles met the inclusion criteria.ConclusionsNSAIDs' effectiveness after SCI is largely determined by its ability to inhibit Rho-A. NSAIDs are a promising therapeutic option in acute SCI patients because they appear to decrease cord edema and inflammation, increase axonal sprouting, and improve motor function with minimal side effects. Studies are limited by heterogeneity, small sample size, and the use of animal models, which might not replicate the therapeutic effects in humans. There are no published human studies evaluating the safety and efficacy of these drugs after a traumatic cord injury. There is a need for well-designed prospective studies evaluating ibuprofen or indomethacin after adult spinal cord injuries.
| S-EPMC8013945 | biostudies-literature
Project description:Spinal cord regeneration after a spinal cord injury (SCI) remains a difficult challenge due to the complicated inflammatory microenvironment and neuronal damage at the injury sites. In this study, retinoic acid (RA) and curcumin (Cur) were co-loaded with bovine serum albumin (BSA) self-assembly to obtain RA@BSA@Cur nanoparticles (NPs) for SCI treatment. Cur, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, and decreased the amount of inflammatory factors secreted by macrophages, while RA could enhance neurite extensions and neural differentiation. The constructed RA@BSA@Cur NPs not only induced polarization of macrophages toward pro-regenerative phenotypes and markedly reduced the inflammatory response of macrophages or microglia, but also increased neurite length in PC12 cells and neuronal differentiation of bone marrow mesenchymal stem cells, improved the differentiation of neural stem cells (NSCs) into β3-tubulin+ neurons, and reversed the pro-astrocyte differentiation effect of inflammatory cytokines on NSCs. In vivo experiments revealed that RA@BSA@Cur NPs regulated the phenotypic polarization of macrophages, inhibited the release of inflammatory mediators, promoted functional neuron regeneration and motor function, and further inhibited scar tissue formation. This study highlighted that the BSA-based biomimetic nanomaterials could be used as ROS scavengers and nerve regeneration promoters for treating SCI.
| S-EPMC9256979 | biostudies-literature
Project description:With advances in genetic and imaging techniques, investigating axon regeneration after spinal cord injury in vivo is becoming more common in the literature. However, there are many issues to consider when using animal models of axon regeneration, including species, strains and injury models. No single particular model suits all types of experiments and each hypothesis being tested requires careful selection of the appropriate animal model. in this review, we describe several commonly-used animal models of axon regeneration in the spinal cord and discuss their advantages and disadvantages.
| S-EPMC3920733 | biostudies-other
Project description:ObjectiveTo test in mice with a double mutation of the ApoE gene (ApoE-/-) whether spinal cord injury (SCI) hastens the native trajectory of, and established component risks for, atherosclerotic disease (AD), and whether Salsalate anti-inflammatory pharmacotherapy attenuates the impact of SCI.MethodsApoE-/- mice were anesthetized and underwent a T9 laminectomy. Exposed spinal cords were given a contusion injury (70 k-dynes). Sham animals underwent all surgical procedures, excluding injury. Injured animals were randomized to 2 groups: SCI or SCI+Salsalate [120 mg/Kg/day i.p.]. Mice were serially sacrificed at 20-, 24-, and 28-weeks post-SCI, and body mass was recorded. At sacrifice, heart and aorta were harvested intact, fixed in 10% buffered formalin, cleaned and cut longitudinally for en face preparation. The aortic tree was stained with oil-red-O (ORO). AD lesion histomorphometry was calculated from the proportional area of ORO. Plasma total cholesterol, triglycerides and proatherogenic inflammatory cytokines (PAIC's) were analyzed.ResultsAD lesion in the aortic arch progressively increased in ApoE-/-, significant at 24- and 28-weeks. AD in SCI is significantly greater at 24- and 28-weeks compared to time-controlled ApoE-/-. Salsalate treatment attenuates the SCI-induced increase at these time points. Body mass in all SCI groups are significantly reduced compared to time-controlled ApoE-/-. Cholesterol and triglycerides are significantly higher with SCI by 24- and 28-weeks, compared to ApoE-/-, and Salsalate reduces the SCI-induced effect on cholesterol. PAIC's interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL-5) are significantly greater with SCI compared to ApoE-/- at varying timepoints. Salsalate confers a marginal reducing effect on PAIC's by 28-weeks compared to SCI. Regression models determine that each PAIC is a significant and positive predictor of lesion. (p's <0.05).ConclusionsSCI accelerates aortic AD and associated risk factors, and anti-inflammatory treatment may attenuate the impact of SCI on AD outcomes. PAIC's IL-1β, IL-6, TNFα, MCP-1, and CCL-5 may be effective predictors of AD.
| S-EPMC7904230 | biostudies-literature
Project description:Trauma to the spinal cord and associated secondary inflammation can lead to permanent loss of sensory and motor function below the injury level, with the resulting environment serving as a barrier that limits regeneration. In this study, we investigate the localized expression of anti-inflammatory cytokines IL-10 and IL-4 via lentiviral transduction in multichannel bridges. Porous multichannel bridges provide physical guidance for axonal outgrowth with the cytokines hypothesized to modulate the neuroinflammatory microenvironment and enhance axonal regeneration. Gene expression analyses indicated that induced IL-10 and IL-4 expression decreased expression of pro-inflammatory genes and increased pro-regenerative genes relative to control. Moreover, these factors led to increased numbers of axons and myelination, with approximately 45% of axons myelinated and the number of oligodendrocyte myelinated axons significantly increased by 3- to 4-fold. Furthermore, the combination of a bridge with IL-10 and IL-4 expression improved locomotor function after injury to an average score of 6 relative to an average score of 3 for injury alone. Collectively, these studies highlight the potential for localized immunomodulation to decrease secondary inflammation and enhance regeneration that may have numerous applications.
| S-EPMC6037204 | biostudies-literature
Project description:Background: Spinal cord injury (SCI) is currently not completely curable. Exosomes have been widely used in preclinical studies of spinal cord injury. Here, in this meta-analysis, we focused on evaluating the overall efficacy of therapies based on miRNA-modified exosomes on functional recovery in animal models of SCI. Methods: PubMed, embase and Web of Science library databases were searched. Relevant literature was included, and the random effects model was used to assess the overall effect of the intervention, with outcomes expressed as SMD. The primary outcome included motor function scores. Risk of bias (ROB) was assessed using the ROB tool of the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). R version 4.1.1software and Review Manager software were used for meta-analysis. Results: A total of 11 preclinical studies were included. The meta-analysis revealed that miRNA-modified exosome therapy was effective in improving motor function scores compared with exosomes alone or control therapy (standardized mean difference: 4.21; 95% confidence interval: 3.39-5.04). There was significant asymmetry in the funnel plot, and trim-and-fill analysis revealed four unpublished studies of motor scores. The quality of all included studies was evaluated with SYRCLE's ROB tool. The SCI model, administration time and dose had an impact on the effect of the treatment. Conclusion: MiRNA-modified exosomes have shown great potential in the treatment of SCI. Moreover, the efficacy of miRNA-modified exosomes was superior to that of exosomes alone.
| S-EPMC8770826 | biostudies-literature
Project description:Spinal cord injury is characterized by initial neural tissue disruption that triggers secondary damage and extensive non-resolving inflammation, which aggravates loss of function and hinders recovery. The early onset of inflammation following traumatic spinal cord injury underscores the importance of acute intervention after the initial trauma. Injections of mesenchymal stromal cells (MSCs) can reduce inflammation following spinal cord injury. We asked if extracellular vesicles (EVs) can substitute the anti-inflammatory and anti-scarring activities of their parental MSCs in a rat model of contusion spinal cord injury. We report that MSC-EVs were as potent as the parental intact cells in reducing the level of neuroinflammation for up to 2 weeks post-injury. Acute application of EVs after spinal cord injury was shown to robustly decrease the expression of pro-inflammatory cytokines in the spinal cord parenchyma in the very early phase of secondary damage. Moreover, the anti-scarring impact of MSC-EVs was even more efficient than the parental cells. We therefore conclude that anti-inflammatory and anti-scarring activities of MSC application can be mediated by their secreted EVs. In light of their substantial safety and druggability advantages, EVs may have a high potential in early therapeutic treatment following traumatic spinal cord injury.
| S-EPMC6896947 | biostudies-literature
Project description:Sexual dysfunction is a common consequence for women with spinal cord injury (SCI); however, current treatments are ineffective, especially in the under-prioritized population of women with SCI. This case-series, a secondary analysis of the Epidural Stimulation After Neurologic Damage (E-STAND) clinical trial aimed to investigate the effect of epidural spinal cord stimulation (ESCS) on sexual function and distress in women with SCI. Three females, with chronic, thoracic, sensorimotor complete SCI received daily (24 h/day) tonic ESCS for 13 months. Questionnaires, including the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale (FSDS) were collected monthly. There was a 3.2-point (13.2%) mean increase in total FSFI from baseline (24.5 ± 4.1) to post-intervention (27.8 ± 6.6), with a 4.8-50% improvement in the sub-domains of desire, arousal, orgasm and satisfaction. Sexual distress was reduced by 55%, with a mean decrease of 12 points (55.4%) from baseline (21.7 ± 17.2) to post-intervention (9.7 ± 10.8). There was a clinically meaningful change of 14 points in the International Standards for Neurological Classification of Spinal Cord Injury total sensory score from baseline (102 ± 10.5) to post-intervention (116 ± 17.4), without aggravating dyspareunia. ESCS is a promising treatment for sexual dysfunction and distress in women with severe SCI. Developing therapeutic interventions for sexual function is one of the most meaningful recovery targets for people with SCI. Additional large-scale investigations are needed to understand the long-term safety and feasibility of ESCS as a viable therapy for sexual dysfunction. Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03026816, NCT03026816.
| S-EPMC10167769 | biostudies-literature
Project description:To investigate the time-dependent changes in expression of cytokines that characterizes the spontaneous recovery of reflex voiding after spinal cord injury (SCI). SCI is known to reorganize the neural circuitry of micturition reflex after injury.Under isoflurane anesthesia, spinal cord of 18 adult female Sprague-Dawley rats was completely transected at the Th9-10 level. Awake cystometry was performed at each time point on controls and 6 SCI animals, and bladder was then harvested for analysis of 29 proteins Millipore kit or enzyme-linked immunosorbent assay. Prophylactic dose of ampicillin 100 mg/kg was administered periodically to all SCI animals.Spontaneous recovery of voiding after SCI at 12 weeks was evident from increased intercontractile interval and voiding efficiency during cystometry. Expression of proinflammatory interleukins ([IL] IL-1? and IL-1?, IL-2, IL-5, IL-6, IL-18, tumor necrosis factor alpha [TNF-?]) and CXC chemokines (CXCL1, CXCL2, CXCL10), CX3CL1, and CCL2 showed significant elevation at 4 and at 8 weeks with slight decrease at 12 weeks. In contrast, expression of anti-inflammatory IL-10 and neuroprotective factors, CXCL-5, and leptin, was elevated at 8 and at 12 weeks (P < .05). In contrast, expression of CCL3, CCL5, and growth factors (vascular endothelial growth factor, nerve growth factor, epidermal growth factor, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor) did not show any significant temporal change after SCI.Spontaneous recovery of reflex voiding at 12 weeks was marked by increased endogenous expression of anti-inflammatory cytokine IL-10 and neuroprotective factors, CXCL-5, and leptin, which suggests that pharmacological suppression of inflammation, can hasten the emergence of reflex voiding after SCI.
| S-EPMC4788527 | biostudies-literature