Hydrogels have been used as promising biomaterials for regeneration and control of pathophysiological events after traumatic spinal cord injuries (TSCI). However, no systematic comparison was ...conducted to show the effect of hydrogels on pathophysiological events. This study was designed to address this issue and evaluate the regenerative potential of hydrogels after TSCI. From 2857 records found in MEDLINE and EMBASE databases (April 23, 2021), 49 articles were included based on our inclusion/exclusion criteria. All studies discussing the effect of hydrogels on at least one of the main pathophysiological events after TSCI, including inflammation, axon growth, remyelination, glial scar formation, cavity size, and locomotor functional recovery were included. For statistical analysis, we used mean difference with 95% confidence intervals for locomotor functional recovery. The results showed that both natural and synthetic hydrogels could reduce the inflammatory response, hinder glial scar formation, and promote axon growth and vascularization. Also, the meta‐analysis of the BBB score showed that using the hydrogels can lead to locomotor functional recovery. It was found that hydrogels are more efficient when used in transection and hemisection injuries (SMD: 1.89; 95% CI: 1.26, 2.52; P < .00001) compared to other injury models. The pre‐formed implanted hydrogels (SMD: 1.79; 95% CI: 1.24, 2.34; P < .00001) found to be more effective compared to injection (SMD: 1.58; 95% CI: 0.64, 2.52; P = 0.0009). In conclusion, based on the available evidence, it was concluded that hydrogel composition as well as implantation method are dominant factors affecting tissue regeneration after TSCI and should be chosen according to the injury model in animal studies.
Background
Microdiscectomy or open discectomy (MD/OD) are the standard procedures for symptomatic lumbar disc herniation and they involve removal of the portion of the intervertebral disc compressing ...the nerve root or spinal cord (or both) with or without the aid of a headlight loupe or microscope magnification. Potential advantages of newer minimally invasive discectomy (MID) procedures over standard MD/OD include less blood loss, less postoperative pain, shorter hospitalisation and earlier return to work.
Objectives
To compare the benefits and harms of MID versus MD/OD for management of lumbar intervertebral discopathy.
Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (November 2013), MEDLINE (1946 to November 2013) and EMBASE (1974 to November 2013) and applied no language restrictions. We also contacted experts in the field for additional studies and reviewed reference lists of relevant studies.
Selection criteria
We selected randomised controlled trials (RCTs) and quasi‐randomised controlled trials (QRCTs) that compared MD/OD with a MID (percutaneous endoscopic interlaminar or transforaminal lumbar discectomy, transmuscular tubular microdiscectomy and automated percutaneous lumbar discectomy) for treatment of adults with lumbar radiculopathy secondary to discopathy. We evaluated the following primary outcomes: pain related to sciatica or low back pain (LBP) as measured by a visual analogue scale, sciatic specific outcomes such as neurological deficit of lower extremity or bowel/urinary incontinence and functional outcomes (including daily activity or return to work). We also evaluated the following secondary outcomes: complications of surgery, duration of hospital stay, postoperative opioid use, quality of life and overall participant satisfaction. Two authors checked data ions and articles for inclusion. We resolved discrepancies by consensus.
Data collection and analysis
We used standard methodological procedures expected by The Cochrane Collaboration. We used pre‐developed forms to extract data and two authors independently assessed risk of bias. For statistical analysis, we used risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI) for each outcome.
Main results
We identified 11 studies (1172 participants). We assessed seven out of 11 studies as having high overall risk of bias. There was low‐quality evidence that MID was associated with worse leg pain than MD/OD at follow‐up ranging from six months to two years (e.g. at one year: MD 0.13, 95% CI 0.09 to 0.16), but differences were small (less than 0.5 points on a 0 to 10 scale) and did not meet standard thresholds for clinically meaningful differences. There was low‐quality evidence that MID was associated with worse LBP than MD/OD at six‐month follow‐up (MD 0.35, 95% CI 0.19 to 0.51) and at two years (MD 0.54, 95% CI 0.29 to 0.79). There was no significant difference at one year (0 to 10 scale: MD 0.19, 95% CI ‐0.22 to 0.59). Statistical heterogeneity was small to high (I2 statistic = 35% at six months, 90% at one year and 65% at two years). There were no clear differences between MID techniques and MD/OD on other primary outcomes related to functional disability (Oswestry Disability Index greater than six months postoperatively) and persistence of motor and sensory neurological deficits, though evidence on neurological deficits was limited by the small numbers of participants in the trials with neurological deficits at baseline. There was just one study for each of the sciatica‐specific outcomes including the Sciatica Bothersomeness Index and the Sciatica Frequency Index, which did not need further analysis. For secondary outcomes, MID was associated with lower risk of surgical site and other infections, but higher risk of re‐hospitalisation due to recurrent disc herniation. In addition, MID was associated with slightly lower quality of life (less than 5 points on a 100‐point scale) on some measures of quality of life, such as some physical subclasses of the 36‐item Short Form. Some trials found MID to be associated with shorter duration of hospitalisation than MD/OD, but results were inconsistent.
Authors' conclusions
MID may be inferior in terms of relief of leg pain, LBP and re‐hospitalisation; however, differences in pain relief appeared to be small and may not be clinically important. Potential advantages of MID are lower risk of surgical site and other infections. MID may be associated with shorter hospital stay but the evidence was inconsistent. Given these potential advantages, more research is needed to define appropriate indications for MID as an alternative to standard MD/OD.
Researchers are trying to study the mechanism of neural stem cells (NSCs) differentiation to oligodendrocyte-like cells (OLCs) as well as to enhance the selective differentiation of NSCs to ...oligodendrocytes. However, the limitation in nerve tissue accessibility to isolate the NSCs as well as their differentiation toward oligodendrocytes is still challenging.
In the present study, a hybrid polycaprolactone (PCL)-gelatin nanofiber scaffold mimicking the native extracellular matrix and axon morphology to direct the differentiation of bone marrow-derived NSCs to OLCs was introduced.
In order to achieve a sustained release of T3, this factor was encapsulated within chitosan nanoparticles and chitosan-loaded T3 was incorporated within PCL nanofibers. Polyaniline graphene (PAG) nanocomposite was incorporated within gelatin nanofibers to endow the scaffold with conductive properties, which resemble the conductive behavior of axons. Biodegradation, water contact angle measurements, and scanning electron microscopy (SEM) observations as well as conductivity tests were used to evaluate the properties of the prepared scaffold. The concentration of PAG and T3-loaded chitosan NPs in nanofibers were optimized by examining the proliferation of cultured bone marrow-derived mesenchymal stem cells (BMSCs) on the scaffolds. The differentiation of BMSCs-derived NSCs cultured on the fabricated scaffolds into OLCs was analyzed by evaluating the expression of oligodendrocyte markers using immunofluorescence (ICC), RT-PCR and flowcytometric assays.
Incorporating 2% PAG proved to have superior cell support and proliferation while guaranteeing electrical conductivity of 10.8 × 10
S/cm. Moreover, the scaffold containing 2% of T3-loaded chitosan NPs was considered to be the most biocompatible samples. Result of ICC, RT-PCR and flow cytometry showed high expression of O4, Olig2, platelet-derived growth factor receptor-alpha (PDGFR-α), O1, myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP) high expressed but low expression of glial fibrillary acidic protein (GFAP).
Considering surface topography, biocompatibility, electrical conductivity and gene expression, the hybrid PCL/gelatin scaffold with the controlled release of T3 may be considered as a promising candidate to be used as an in vitro model to study patient-derived oligodendrocytes by isolating patient's BMSCs in pathological conditions such as diseases or injuries. Moreover, the resulted oligodendrocytes can be used as a desirable source for transplanting in patients.
It remains unclear whether biomarkers in the serum or CSF can be used for diagnosis or prognosis of spinal cord injuries (SCI). Therefore, a systematic review was undertaken to evaluate the ...prognostic or diagnostic value of serum and CSF biomarkers in assessing the severity of SCI and the outcome of patients. Two independent reviewers summarized the human studies retrieved from the electronic databases of Medline, Embase, Scopus and ISI Web of Science until April 2018. Seventeen studies were included (1065 patients aged 16–94 years old). Although the findings of the included studies suggest that inflammatory and structural proteins may be useful in assessing the severity of SCI and prediction of neurological outcome, the level of evidence is generally low. Given limitations to the available evidence, further investigation in this field is required using large prospective data sets with rigorous analysis of sensitivity, specificity and prediction.
Inflammatory and structural proteins may be useful in assessing the severity of spinal cord injury and prediction of neurological outcome. After the injury, the serum and cerebrospinal fluid levels of IL‐1β, IL‐5, IL‐17 and IGF‐1 drop while the concentration of IL‐6, Il‐10, IL‐16, IL‐18, CXCL‐1, CXCL‐9, CXCL‐10, CXCL‐12, and MIF increases. A significant rise also occurs in the levels of the structural proteins MMP‐8, GFAP, neurofilaments, NSE, S100‐β and HMGB1.
Purpose
Traumatic spinal cord injuries (TSCI) are among the most devastating conditions in developed and developing countries, which can be prevented. The situation of TSCI around the world is not ...well understood which complicates the preventive policy decision making in fight against TSCI. This study was aimed to gather the available information about incidence of TSCI around the world.
Methods
A systematic search strategy was designed and run in Medline and EMBASE, along with extensive grey literature search, personal communications, website searching, and reference checking of related papers.
Results
Overall, 133 resources including 101 papers, 17 trauma registries, 6 conference proceedings, 5 books, 2 theses and 2 personal communication data were retrieved. Data were found for 41 individual countries. The incidence of TSCI ranges from 3.6 to 195.4 patients per million around the world. Australia, Canada, US, and high-income European countries have various valuable reports of TSCI, while African and Asian countries lack the appropriate epidemiologic data on TSCI.
Conclusion
Data of epidemiologic information in TSCI are available for 41 countries of the world, which are mostly European and high-income countries. Researches and efforts should be made to gather information in developing and low-income countries to plan appropriate cost-effective preventive strategies in fight against TSCI.
Spinal cord regeneration is limited due to various obstacles and complex pathophysiological events after injury. Combination therapy is one approach that recently garnered attention for spinal cord ...injury (SCI) recovery. A composite of three-dimensional (3D) collagen hydrogel containing epothilone B (EpoB)-loaded polycaprolactone (PCL) microspheres (2.5 ng/mg, 10 ng/mg, and 40 ng/mg EpoB/PCL) were fabricated and optimized to improve motor neuron (MN) differentiation efficacy of human endometrial stem cells (hEnSCs). The microspheres were characterized using liquid chromatography-mass/mass spectrometry (LC-mas/mas) to assess the drug release and scanning electron microscope (SEM) for morphological assessment. hEnSCs were isolated, then characterized by flow cytometry, and seeded on the optimized 3D composite. Based on cell morphology and proliferation, cross-linked collagen hydrogels with and without 2.5 ng/mg EpoB loaded PCL microspheres were selected as the optimized formulations to compare the effect of EpoB release on MN differentiation. After differentiation, the expression of MN markers was estimated by real-time PCR and immunofluorescence (IF). The collagen hydrogel containing the EpoB group had the highest HB9 and ISL-1 expression and the longest neurite elongation. Providing a 3D permissive environment with EpoB, significantly improves MN-like cell differentiation and maturation of hEnSCs and is a promising approach to replace lost neurons after SCI.
Microtubule‐stabilizing agents (MSAs), until now, have primarily been considered for their anti‐proliferative effects in the setting of cancer. However, recent studies have revealed that one ...particular MSA, epothilone B (EpoB), can promote axonal regeneration after traumatic spinal cord injuries (SCI) even in the presence of inhibitor molecules such as neurite outgrowth inhibitor‐A (Nogo‐A). On the basis of the importance of having an efficient motor neuron (MN) differentiation protocol for stem cell therapy and the attention of MSAs for SCI treatment, our study investigated the effect of EpoB on human endometrial stem cells (hEnSCs) differentiation into MN‐like cells. hEnSCs were isolated and characterized by flow cytometry. The hEnSC cell viability was evaluated by a 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. To mimic the in vivo inhibitory environment, hEnSCs were also differentiated in the presence of Nogo‐A. After 15 days of differentiation, the expressions of MN‐markers were evaluated by real‐time reverse‐transcriptase polymerase chain reaction and immunofluorescence. According to the MTT assay results, three doses (1, 5, and 10 nM) of EpoB were selected to evaluate their effect on MN‐differentiation. All selected doses can increase the efficacy of hEnSCs differentiation into MN‐like cells. In particular, the 10 nM EpoB dosage was shown to increase the axon elongation, cell alignment, and upregulation of these MN‐markers compared with other doses. EpoB can improve MN differentiation from hEnSC and potentially provide a unique route for neuronal replacement in the setting of SCI.
Purpose： Traumatic brain injury （TBI） is a leading cause of death and disability, lntracranial hemorrhage （ICH） secondary to TBI is associated with a high risk of coagulopathy which leads to ...increasing risk of hemorrhage growth and higher mortality rate. Therefore, antifibrinolytic agents such as tranexamic acid （TA） might reduce traumatic ICH. The aim of the present study was to investigate the extent of ICH growth after TA administration in TBI patients. Methods： This single-blind randomized controlled trial was conducted on patients with traumatic ICH （with less than 30 ml） referring to the emergency department of Vali-Asr Hospital, Arak, Iran in 2014. Patients, based on the inclusion and exclusion criteria, were divided into intervention and control groups （40 patients each）. All patients received a conservative treatment for ICH, as well as either intravenous TA or placebo. The extent of ICH growth as the primary outcome was measured by brain cr scan after 48 h. Results： Although brain CT scan showed a significant increase in hemorrhage volume in both groups after 48 h, it was significantly less in the TA group than in the control group （p = 0.04）. The mean total hemorrhage expansion was （1.7 ± 9.7） ml and （4.3 ± 12.9） ml in TA and placebo groups, respectively （p 〈 0.001）. Conclusion： It has been established that TA, as an effective hospital-based treatment for acute TBI, could reduce ICH growth. Larger studies are needed to compare the effectiveness of different doses.
Purpose
To gain insight into current research regarding prehospital care (PHC) in patients with potential traumatic spinal cord injury (TSCI) and to disseminate the findings to the research ...community.
Methods
In March 2019, we performed a literature search of publications from January 1990 to March 2019 indexed in PubMed, gray literature including professional websites; and reference sections of selected articles for other relevant literature. This review was performed according to Arksey and O’Malley’s framework.
Results
There were 42 studies selected based on the inclusion criteria for review; 18 articles regarding immobilization; 12 articles regarding movement, positioning and transport; four for spinal clearance; three for airway protection; and two for the role of PHC providers. There were some articles that covered two topics: one article was regarding movement, positioning and transport and airway protection, and two were regarding spinal clearance and the role of PHC providers.
Conclusion
There was no uniform opinion about spinal immobilization of patients with suspected TSCI. The novel lateral trauma position and one of two High Arm IN Endangered Spine (HAINES) methods are preferred methods for unconscious patients. Controlled self-extrication for patients with stable hemodynamic status is recommended. Early and proper identifying of potential TSCI by PHC providers can significantly improve patients’ outcomes and can result in avoiding unwanted spinal immobilization. Future prospective studies with a large sample size in real-life settings are needed to provide clear and evidence-based data in PHC of patients with suspected TSCI.
This study was designed to determine the effective therapeutic parameters and evaluate the regenerative potential of low-level laser therapy (LLLT) after traumatic spinal cord injuries (TSCIs) in ...animal studies. The EMBASE and MEDLINE databases were searched on October 5, 2019, and followed with an update on January 2, 2021. All animal studies discussing the effect of LLLT on main pathophysiological events after TSCI, including inflammation, axon growth, remyelination, glial scar formation, cavity size, and locomotor recovery, were included. For statistical analysis, we used mean difference with 95% confidence intervals for locomotor recovery. In total, 19 articles were included based on our criteria. The results showed that regardless of laser type, laser beams with a wavelength between 600 and 850 nm significantly suppress inflammation and led inflammatory cells to M2 polarization and wound healing. Also, laser therapy using these wavelengths for more than 2 weeks significantly improved axon regeneration and remyelination. Improvement of locomotor recovery was more efficient using wavelengths less than 700 nm (SMD = 1.21; 95%CI: 0.09, 2.33;
p
= 0.03), lasers with energy densities less than 100 J/cm
2
(SMD = 1.72; 95%CI: 0.84, 2.59;
p
= 0.0001) and treatment duration between 1 and 2 weeks (SMD = 2.21; 95%CI: 1.24, 3.19;
p
< 0.00001). The LLLT showed promising potential to modulate pathophysiological events and recovery after TSCI, although there was heterogeneity in study design and reporting methods, which should be considered in future studies.
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