Strategy For Spinal Cord Injury Research Articles

MicroRNA-34c promotes neuronal recovery in rats with spinal cord injury through the C-X-C motif ligand 14/Janus kinase 2/signal transducer and activator of transcription-3 axis.

Developing effective spinal cord repair strategies for spinal cord injury (SCI) is of great importance. Emerging evidence suggests that microRNAs (miRNAs) are closely linked to SCI recovery. This study aimed to investigate the function of miR-34c in the neuronal recovery in rats with SCI. A rat model with SCI was established. Differentially expressed miRNAs were identified by a microarray analysis. MiR-34c expression in rats was measured by reverse transcription quantitative polymerase chain reaction. Altered expression of miR-34c or C-X-C motif ligand 14 (CXCL14) was introduced in SCI rats to measure their roles in neuronal recovery. Western blot analysis was performed to determine the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription-3 (STAT3). Neuronal apoptosis in rat spinal cord tissues was detected. The concentrations of SCI recovery-related proteins thyrotropin releasing hormone (TRH), prostacyclin (PGI2), and ganglioside (GM) were evaluated by enzyme-linked immunosorbent assay. Data were analyzed using a t-test with a one-way or two-way analysis of variance. Rats with SCI presented decreased grip strength (112.03 ± 10.64 vs. 17.32 ± 1.49 g, P < 0.01), decreased miR-34c expression (7 days: 3.78 ± 0.44 vs. 0.95 ± 0.10, P < 0.05), and increased CXCL14 expression (7 days: 0.61 ± 0.06 vs. 2.91 ± 0.27, P < 0.01). MiR-34c was found to directly bind to CXCL14. Overexpression of miR-34c increased grip strength (11.23 ± 1.08 vs. 31.26 ± 2.99 g, P < 0.01) and reduced neuronal apoptosis in spinal cord tissues (53.61% ± 6.07% vs. 24.59% ± 3.32%, P < 0.01), and silencing of CXCL14 also increased the grip strength (12.76 ± 1.13 vs. 29.77 ± 2.75 g, P < 0.01) and reduced apoptosis in spinal cord tissues (55.74% ± 6.24% vs. 26.75% ± 2.84%, P < 0.01). In addition, miR-34c upregulation or CXCL14 downregulation increased the concentrations of TRH, PGI2, and GM, and reduced phosphorylation of JAK2 and STAT3 in rats with SCI (all P < 0.01). The study provided evidence that miR-34c could promote neuronal recovery in rats with SCI through inhibiting CXCL14 expression and inactivating the JAK2/STAT3 pathway. This study may offer new insights into SCI treatment.

Transplantation Strategies for Spinal Cord Injury Based on Microenvironment Modulation.

Spinal cord injury (SCI) is different from peripheral nerve injury; it results in devastating and permanent damage to the spine, leading to severe motor, sensory and autonomic dysfunction. SCI produces a complex microenvironment that can result in hemorrhage, inflammation and scar formation. Not only does it significantly limit regeneration, but it also challenges a multitude of transplantation strategies. In order to promote regeneration, researchers have recently begun to focus their attention on strategies that manipulate the complicated microenvironment produced by SCI. And some have achieved great therapeutic effects. Hence, reconstructing an appropriate microenvironment after transplantation could be a potential therapeutic solution for SCI. In this review, first, we aim to summarize the influential compositions of the microenvironment and their different effects on regeneration. Second, we highlight recent research that used various transplantation strategies to modulate different microenvironments produced by SCI in order to improve regeneration. Finally, we discuss future transplantation strategies regarding SCI.

Regulation of autophagy in mesenchymal stem cells modulates therapeutic effects on spinal cord injury

Transplantation with mesenchymal stem cells (MSCs) has shown beneficial effects in treating spinal cord injury. Autophagy is an evolutionarily conserved process of degradation and recycling of cellular components that plays an important role in tissue homeostasis and cellular survival. Whether regulating autophagy in MSCs may affect their therapeutic potential in spinal cord injury repair has not yet been determined. In this study, autophagy was inhibited in MSCs with lentiviruses expressing short hairpin RNA (shRNA) to knock down Becn-1 expression, and autophagy was upregulated in MSCs under nutrient starvation. These MSCs were then labelled with Hoechst and applied to spinal cord-injured rats to evaluate their therapeutic effects. After transplanting MSCs into rats with spinal cord injuries, functional recovery, immunohistochemistry, and remyelination analyses were performed. After inducing autophagy, the MSCs exhibited an accumulation of LC3-positive autophagosomes in the cytoplasm. The expression levels of neurotrophic factors, including vascular endothelial growth factor and brain derived neurotrophic factor, were significantly higher in autophagic MSCs than normal MSCs. The in vivo study showed that more labelled MSCs migrated to the lesion site after induction of autophagy. Inducing autophagy in MSCs promoted functional recovery after spinal cord injury, whereas functional recovery was weak after inhibiting autophagy in MSCs. In contrast to the autophagy inhibition group, transplanting autophagic MSCs exhibited a greater positive impact on axon regeneration, growth of serotonergic fibers, blood vessel regeneration, and myelination, indicating a multifactorial contribution to spinal cord injury repair. These results suggest that autophagy plays important roles in MSCs during spinal cord injury repair. Regulation of autophagy in MSCs before in vivo transplantation may be a potential therapeutic interventional strategy for spinal cord injury.

Nucleic Acid Vaccine Targeting Nogo-66 Receptor and Paired Immunoglobulin-Like Receptor B as an Immunotherapy Strategy for Spinal Cord Injury in Rats.

Nogo-66 receptor (NgR) and paired immunoglobulin-like receptor B (PirB) are two common receptors of various myelin-associated inhibitors (MAIs) and, thus, play an important role in MAIs-induced inhibitory signalling of regeneration following spinal cord injury (SCI). Based on the concept of protective autoimmunity, vaccine approaches could induce the production of antibodies against inhibitors in myelin, such as using purified myelin, spinal cord homogenates, or MAIs receptor NgR, in order to block the inhibitory effects and promote functional recovery in SCI models. However, due to the complication of the molecules and the mechanisms involved in MAIs-mediated inhibitory signalling, these immunotherapy strategies have yielded inconsistent outcomes. Therefore, we hypothesized that the choice and modification of self-antigens, and co-regulating multiple targets, may be more effective in repairing the injured spinal cord and improving functional recovery. In this study, NgR and PirB were selected to construct a double-targeted granulocyte-macrophage colony stimulating factor-NgR-PirB (GMCSF-NgR-PirB) nucleic acid vaccine, and investigate the efficacy of this immunotherapy in a spinal cord injury model in rats. The results showed that this vaccination could stimulate the production of antibodies against NgR and PirB, block the inhibitory effects mediated by various MAIs, and promote nerve regeneration and functional recovery after spinal cord injury. These findings suggest that nucleic acid vaccination against NgR and PirB can be a promising therapeutic strategy for SCI and other central nervous system diseases and injuries.

Is cell transplantation a reliable therapeutic strategy for spinal cord injury in clinical practice? A systematic review and meta-analysis from 22 clinical controlled trials.

It is an open question whether cell transplantation can provide safety and effective outcome to spinal cord injury (SCI) patient which has remained controversial for almost 40years. This study aimed to evaluate the safety and efficacy of cell transplantation in SCI patients. Studies of the cell transplantation for SCI were retrieved from PubMed, Embase, Medline, Cochrane Library and analyzed quantitative data by Review Manager 5.3. Twenty-one clinical controlled studies with 973 patients were included. The pooled results suggested that cell transplantation significantly improved ASIA score, ASIA motor score, ASIA sensory score, Barthel Index score, residual urine volume, rehabilitative time of automatic micturition. Furthermore, subgroup analysis indicated that the stem cells exhibited more potent than the non-stem cells in spinal cord repair. Cell transplantation at more than 14days after injury showed more significant improvements than that within 14days from injury. The dosage of cell transplantation between 1-5 × 107 and 10-20 × 107 was the potent quantity for the patient with SCI. Intrathecal injection and intravenous + intrathecal injection showed more superior to the other method. The top 5 adverse events were febrile reaction (11.5%), neurologic pain (11.3%), headache (2.6%), neurologic deterioration (2.4%), and rigidity or spasticity (1.6%). Cell transplantation appears to be a safe therapeutic strategy possessing substantial beneficial effects in the patients with SCI in clinic. Moreover, treating SCI with stem cell, the dosage of cells between 1-5 × 107 and 10-20 × 107, in intermediate or chronic phase, minimally invasive techniques, may bring more advantage to SCI patient. These slides can be retrieved under Electronic Supplementary Material.

E-cadherin regulates biological behaviors of neural stem cells and promotes motor function recovery following spinal cord injury.

Stem cell-based repair strategies for spinal cord injury (SCI) are a highly studied area of research. Multiple gene-modified stem cells have been transplanted into SCI models, in the hope of generating more neurons to repair a damaged nervous system. However, the results are not always successful, as the grafted cells may be unable to survive in the injured spinal cord. E-cadherin, a transmembrane adhesion protein, has been identified as an epithelial-to-mesenchymal transition marker and is vital for morphological structure maintenance and the functional integrity of epithelial cells. At present, few studies have examined the association between E-cadherin and neural stem cells (NSCs). The present study investigated the expression of E-cadherin in subcultured NSCs and differentiated NSCs. Furthermore, the effect of E-cadherin on NSC viability, migration, differentiation and neurosphere formation was assessed. An in vivo study was used to assess the long-term survival of grafted NSCs. Additionally, the protective effect of E-cadherin on SCI was assessed by analyzing tissue repair, Basso Mouse Scale scores and the expression of inflammatory cytokines. The results of the present study suggested that E-cadherin was able to promote NSC viability and neurosphere formation; however, it had no significant effect on NSC differentiation. To conclude, grafted NSCs with highly expressed E-cadherin facilitated motor function recovery following SCI by reducing the release of inflammatory cytokines.

Automated Gait Analysis Detects Improvements after Intracellular σ Peptide Administration in a Rat Hemisection Model of Spinal Cord Injury.

A promising treatment strategy for spinal cord injury (SCI) is to reduce inhibition from chondroitin sulfate proteoglycans (CSPGs). For example, administering intracellular σ peptide (ISP) can improve the ability of axons to cross inhibitory CSPGs and improve function in rodent models of SCI. To translate such treatments into the clinic, we need robust and sensitive methods for studying rodent models. In this study, we applied a newly developed suite of quantitative gait analysis tools: gait analysis instrumentation and technology optimized for rodents (GAITOR), which consists of an arena and open-source software (AGATHA: automated gait analysis through hues and areas). We showed that GAITOR can be used to detect subtle functional improvements (measured by hindlimb duty factor imbalance) in rats following ISP administration in a T10 hemisection injury model. We demonstrated that SCI-specific parameters (right paw placement accuracy and phase dispersion) can be easily added to GAITOR to track recovery. We confirmed the gait observations via retrograde tracer uptake. We concluded that GAITOR is a powerful tool for measuring recovery after moderate/mild SCI, and could be used to replace expensive/inflexible commercially-available gait analysis techniques.

Mesenchymal stem cells and the neuronal microenvironment in the area of spinal cord injury.

Cell-based technologies are used as a therapeutic strategy in spinal cord injury (SCI). Mesenchymal stem cells (MSCs), which secrete various neurotrophic factors and cytokines, have immunomodulatory, anti-apoptotic and anti-inflammatory effects, modulate reactivity/phenotype of astrocytes and the microglia, thereby promoting neuroregeneration seem to be the most promising. The therapeutic effect of MSCs is due to a paracrine mechanism of their action, therefore the survival of MSCs and their secretory phenotype is of particular importance. Nevertheless, these data are not always reported in efficacy studies of MSC therapy in SCI. Here, we provide a review with summaries of preclinical trials data evaluating the efficacy of MSCs in animal models of SCI. Based on the data collected, we have tried (1) to establish the behavior of MSCs after transplantation in SCI with an evaluation of cell survival, migration potential, distribution in the area of injured and intact tissue and possible differentiation; (2) to determine the effects MSCs on neuronal microenvironment and correlate them with the efficacy of functional recovery in SCI; (3) to ascertain the conditions under which MSCs demonstrate their best survival and greatest efficacy.

Astrocyte progenitor transplantation promotes regeneration of bulbospinal respiratory axons, recovery of diaphragm function, and a reduced macrophage response following cervical spinal cord injury.

Stem/progenitor cell transplantation delivery of astrocytes is a potentially powerful strategy for spinal cord injury (SCI). Axon extension into SCI lesions that occur spontaneously or in response to experimental manipulations is often observed along endogenous astrocyte "bridges," suggesting that augmenting this response via astrocyte lineage transplantation can enhance axon regrowth. Given the importance of respiratory dysfunction post-SCI, we transplanted glial-restricted precursors (GRPs)-a class of lineage-restricted astrocyte progenitors-into the C2 hemisection model and evaluated effects on diaphragm function and the growth response of descending rostral ventral respiratory group (rVRG) axons that innervate phrenic motor neurons (PhMNs). GRPs survived long term and efficiently differentiated into astrocytes in injured spinal cord. GRPs promoted significant recovery of diaphragm electromyography amplitudes and stimulated robust regeneration of injured rVRG axons. Although rVRG fibers extended across the lesion, no regrowing axons re-entered caudal spinal cord to reinnervate PhMNs, suggesting that this regeneration response-although impressive-was not responsible for recovery. Within ipsilateral C3-5 ventral horn (PhMN location), GRPs induced substantial sprouting of spared fibers originating in contralateral rVRG and 5-HT axons that are important for regulating PhMN excitability; this sprouting was likely involved in functional effects of GRPs. Finally, GRPs reduced the macrophage response (which plays a key role in inducing axon retraction and limiting regrowth) both within the hemisection and at intact caudal spinal cord surrounding PhMNs. These findings demonstrate that astrocyte progenitor transplantation promotes significant plasticity of rVRG-PhMN circuitry and restoration of diaphragm function and suggest that these effects may be in part through immunomodulation.

Neuroprotection by Paeoniflorin against Nuclear Factor Kappa B-Induced Neuroinflammation on Spinal Cord Injury.

Background Acute spinal cord injury (SCI) is one of the most common and devastating causes of sensory or motor dysfunction. Nuclear factor-kappa B(NF-κB)-mediated neuroinflammatory responses, in addition to nitric oxide (NO), are key regulatory pathways in SCI. Paeoniflorin (PF), a major active component extracted from Paeonia roots, has been suggested to exert neuroprotective effects in the central nervous system. However, whether PF could improve the motor function after SCI in vivo is still unclear. Method Immunohistochemical analysis, western blot, real-time quantitative PCR, immunofluorescence staining, and histopathological and behavioral evaluation were used to explore the effects of paeoniflorin after SCI for 14 days. Results In this study, PF treatment significantly inhibited NF-κB activation and downregulated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2(COX-2), and Nogo-A. Comparing behavioral and histological changes in SCI and PF treatment groups, we found that PF treatment improved motor function recovery, attenuated the histopathological damage, and increased neuronal survival in the SCI model. PF treatment also reduced expression levels of Bax and c-caspase-3 and increased the expression level of Bcl-2 and cell viabilities. Upregulation of TNF-α, IL-6, and IL-1β after injury was also prevented by PF. Conclusion These results suggest that the neuroprotective effects of PF are related to the inhibition of the NF-κB signaling pathway. And PF may be a therapeutic strategy in spinal cord injury.

Anti-Chondroitin Sulfate Proteoglycan Strategies in Spinal Cord Injury: Temporal and Spatial Considerations Explain the Balance between Neuroplasticity and Neuroprotection

Abstract Loss of function after spinal cord injury (SCI) results from the primary injury that causes interruption of axonal tracts, neuronal and glial cell death, and the secondary injury in which ...

Decellularized peripheral nerve supports Schwann cell transplants and axon growth following spinal cord injury

Schwann cell (SC) transplantation has been comprehensively studied as a strategy for spinal cord injury (SCI) repair. SCs are neuroprotective and promote axon regeneration and myelination. Nonetheless, substantial SC death occurs post-implantation, which limits therapeutic efficacy. The use of extracellular matrix (ECM)-derived matrices, such as Matrigel, supports transplanted SC survival and axon growth, resulting in improved motor function. Because appropriate matrices are needed for clinical translation, we test here the use of an acellular injectable peripheral nerve (iPN) matrix. Implantation of SCs in iPN into a contusion lesion did not alter immune cell infiltration compared to injury only controls. iPN implants were larger and contained twice as many SC-myelinated axons as Matrigel grafts. SC/iPN animals performed as well as the SC/Matrigel group in the BBB locomotor test, and made fewer errors on the grid walk at 4 weeks, equalizing at 8 weeks. The fact that this clinically relevant iPN matrix is immunologically tolerated and supports SC survival and axon growth within the graft offers a highly translational possibility for improving efficacy of SC treatment after SCI. To our knowledge, it is the first time that an injectable PN matrix is being evaluated to improve the efficacy of SC transplantation in SCI repair.

PPAR-γ Agonist Promotes Proliferation of Neural Stem Cells Via Mitophagy Inhibition

Background: Proliferation of neural stem cells (NSCs) is crucial for recovery from spinal cord injury (SCI). The effect of PPAR-γ agonist on SCI recovery and the way it regulating NSCs proliferation are both unknown. Methods: The effects of PPAR-γ agonist (rosiglitazone) treatment on recovery from SCI and proliferation of NSCs were confirmed. The roles of mitophagy and PTEN induced putative kinase 1 (PINK1) in rosiglitazoneinduced proliferation of NSCs were explored. Details mechanisms on the transcription regulation of PINK1 by rosiglitazone were addressed. Findings: Rosiglitazone independently increased the proportion of Nestin /Brdu cells in the spinal cord and motor function of SCI rats. It reduced mitophagy and expression of PTEN induced putative kinase 1 (PINK1) in NSCs. The forkhead box protein O1 (FOXO1) was identified as the transcription factor mostly altered by rosiglitazone. Restoration of FOXO1 expression antagonized the effects of rosiglitazone on mitophagy and PINK1 expression. The FOXO1 consensus sequence (FCS) was not identified upstream of the PINK1 transcription start site, but three FCSs were found in the first intron of the PINK1 gene. All of the FCSs participated in the regulation of PINK1 transcription upon treatment with rosiglitazone and expression of FOXO1 but the proximal FCS (chr 5: 156680169-156680185, 3022 bp counting from the translation start site) exerted greater influence. Conclusions: PPAR-γ agonist could be a promising therapeutic strategy for spinal cord injury. Funding Statement:This work was supported by the National Natural Science Foundation of China (Grant No. 81870334, 81301038, 81300071, 81300279 and 81741067); the Science and Technology Program of Guangdong (Grant No. 2015A020212029); and the Science and Technology Program of Guangzhou City (Grant No. 201510010048, 201607010009, 201607010010 and 201804010050). Declaration of Interests: All authors declare no potential conflict of interest. Ethics Approval Statement: All of the animal experiments complied with the ARRIVE guidelines, and they were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publication No. 8023, revised 1978)

Integrated data analysis identifies potential inducers and pathways during the endothelial differentiation of bone-marrow stromal cells by DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine

Bone-Marrow Stromal Cells (BMSCs)-derived vascular endothelial cells (VECs) is regarded as an important therapeutic strategy for spinal cord injury, disc degeneration, cerebral ischemic disease and diabetes. The change in DNA methylation level is essential for stem cell differentiation. However, the DNA methylation related mechanisms underlying the endothelial differentiation of BMSCs are not well understood. In this study, DNA methyltransferase inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC) significantly elevated the endothelial markers expression (CD31/PECAM1, CD105/ENG, eNOS and VE-cadherin), as well as promoted the capacity of angiogenesis on Matrigel. The result of Alexa 488-Ac-LDL uptake assay indicated that the differentiation ratio of BMSCs into VECs was 68.7% in 5-azaz-dC induced differentiation. And then we screened differentiation inducers with altered expression patterns and DNA methylation levels in four important families (VEGF, ANG, FGF and ETS). By integrating these data, five endothelial differentiation inducers (VEGFA, ANGPT2, FGF2, FGF9 and ETS1) which were directly upregulated by 5-aza-dC and five indirect factors (FGF1, FGF3, ETS2, ETV1 and ETV4) were identified. These data suggested that 5-aza-dC is an excellent chemical molecule for BMSCs differentiation into functional VECs and also provided essential clues for DNA methylation related signaling during 5-aza-dC induced endothelial differentiation of BMSCs.

Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate-Induced Excitotoxicity.

New treatment strategies for spinal cord injury with good therapeutic efficacy are actively pursued. Here, acetalated dextran (AcDX), a biodegradable polymer obtained by modifying vicinal diols of dextran, is demonstrated to protect the traumatically injured spinal cord. To facilitate its administration, AcDX is formulated into microspheres (≈7.2 µm in diameter) by the droplet microfluidic technique. Intrathecally injected AcDX microspheres effectively reduce the traumatic lesion volume and inflammatory response in the injured spinal cord, protect the spinal cord neurons from apoptosis, and ultimately, recover the locomotor function of injured rats. The neuroprotective feature of AcDX microspheres is achieved by sequestering glutamate and calcium ions in cerebrospinal fluid. The scavenging of glutamate and calcium ion reduces the influx of calcium ions into neurons and inhibits the formation of reactive oxygen species. Consequently, AcDX microspheres attenuate the expression of proapoptotic proteins, Calpain, and Bax, and enhance the expression of antiapoptotic protein Bcl-2. Overall, AcDX microspheres protect traumatically injured spinal cord by alleviating the glutamate-induced excitotoxicity. This study opens an exciting perspective toward the application of neuroprotective AcDX for the treatment of severe neurological diseases.

Study protocol: patient reported outcomes for bladder management strategies in spinal cord injury

BackgroundThe majority of spinal cord injury (SCI) patients have urinary issues, such as incontinence, retention, and frequency. These problems place a significant burden on patients’ physical health and quality of life (QoL). There are a wide variety of bladder management strategies available to patients with no clear guidelines on appropriate selection. Inappropriate bladder management can cause hospitalizations and serious complications, such as urosepsis and renal failure. Patients believe that both independence and ability to carry out daily activities are just as important as physical health in selecting the right bladder-management strategy but little is known about patient’s QoL with different bladder managements. Our study’s aim is to assess patient reported QoL measures with various bladder managements after SCI. This manuscript describes the approach, study design and common data elements for our central study.MethodsThis is a multi-institutional prospective cohort study comparing three different bladder-management strategies (clean intermittent catheterization, indwelling catheters, and surgery). Information collected from participants includes demographics, past medical and surgical history, injury characteristics, current and past bladder management, and SCI /bladder-related complications. Patient reported outcomes and QoL questionnaires were administered at enrollment and every 3 months for 1 year. Aims of this study protocol are: (1) to assess baseline QoL differences between the three different bladder-management strategies; (2) determine QoL impact when those using either form of catheter management undergo a surgery over the 1 year of follow-up among patients eligible for surgery; (3) assess the effects of changes in bladder management and complications on QoL over a 1-year longitudinal follow-up.DiscussionBy providing information about patient-reported outcomes associated with different bladder management strategies after SCI, and the impact of bladder management changes and complications on QoL, this study will provide essential information for shared decision-making and guide future investigation.Trial registrationTrial registration number: www.clinicaltrials.gov: Identifier: NCT0261608; U.S. National Library of Medicine, wwwcf.nlm.nih.gov: Identifier: HSRP20153564.

Ibuprofen-loaded fibrous patches-taming inhibition at the spinal cord injury site.

It is now widely accepted that a therapeutic strategy for spinal cord injury (SCI) demands a multi-target approach. Here we propose the use of an easily implantable bilayer polymeric patch based on poly(trimethylene carbonate-co-ε-caprolactone) (P(TMC-CL)) that combines physical guidance cues provided by electrospun aligned fibres and the delivery of ibuprofen, as a mean to reduce the inhibitory environment at the lesion site by taming RhoA activation. Bilayer patches comprised a solvent cast film onto which electrospun aligned fibres have been deposited. Both layers were loaded with ibuprofen. In vitro release (37°C, in phosphate buffered saline) of the drug from the loaded scaffolds under sink condition was found to occur in the first 24 h. The released ibuprofen was shown to retain its bioactivity, as indicated by the reduction of RhoA activation when the neuronal-like cell line ND7/23 was challenged with lysophosphatidic acid. Ibuprofen-loaded P(TMC-CL) bilayer scaffolds were successfully implanted in vivo in a dorsal hemisection rat SCI model mediating the reduction of RhoA activation after 5 days of implantation in comparison to plain P(TMC-CL) scaffolds. Immunohistochemical analysis of the tissue shows βIII tubulin positive cells close to the ibuprofen-loaded patches further supporting the use of this strategy in the context of regeneration after a lesion in the spinal cord.

Meta-analysis of stem cell transplantation for reflex hypersensitivity after spinal cord injury

Stem cells have been used in novel therapeutic strategies for spinal cord injury (SCI), but the effect of stem cell transplantation on neuropathic pain after SCI is unclear. The current meta-analysis evaluates the effects of stem cell transplantation on neuropathic pain after SCI. We first conducted online searches of PubMed, Web of Science, China Academic Journals Full-text Database, and Wanfang Data for randomized controlled trials that compared stem cell transplantation and vehicle treatments in rodent models of neuropathic pain after SCI. Quality assessment was performed using Cochrane Reviewer’s Handbook 5.1.0, and meta-analysis was conducted with RevMan 5.3. Then, we developed a rat model of SCI and transplanted bone marrow mesenchymal stem cells to verify meta-analysis results. Twelve randomized, controlled trials (n=354 total animals) were included in our meta-analysis and divided by subgroups, including species, timing of behavioral measurements, and transplantation time after SCI. Subgroup analysis of these 12 studies indicated that stem cell-treated animals had a higher mechanical reflex threshold than vehicle groups, with a significant difference in both rats and mice. The thermal withdrawal latency showed the same results in mouse subgroups, but not in rat subgroups. In addition, mesenchymal stem cell transplantation was an effective treatment for mechanical, but not thermal reflex hypersensitivity relief in rats. Transplantation showed a positive effect when carried out at 3 or 7days post-SCI. Stem cell transplantation alleviates mechanical reflex hypersensitivity in rats and mice and thermal reflex hypersensitivity in mice after SCI.

Update on traumatic acute spinal cord injury. Part 2

The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers).

Actualización en lesión medular aguda postraumática. Parte 2

The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers).