Oligodendrogliogenesis and axon remyelination after traumatic spinal cord injuries in animal studies: a systematic review

© 2019 IBRO Extensive oligodendrocyte death after acute traumatic spinal cord injuries (TSCI) leads to axon demyelination and subsequently may leave axons vulnerable to degeneration. Despite the present evidence showing spontaneous remyelination after TSCI the cellular origin of new myelin and the time course of the axon ensheathment/remyelination remained controversial issue. In this systematic review the trend of oligodendrocyte death after injury as well as the extent and the cellular origin of oligodendrogliogenesis were comprehensively evaluated. The study design was based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-guided systematic review. PubMed and EMBASE were searched with no temporal or linguistic restrictions. Also, hand-search was performed in the bibliographies of relevant articles. Non-interventional animal studies discussing different types of myelinating cells including oligodendrocytes, Schwann cells and oligodendrocyte progenitor cells (OPCs) were evaluated. The extent of oligodendrocyte death, oligodendrocyte differentiation and remyelination were the pathophysiological outcome measures. We found 12,359 studies, 34 of which met the inclusion criteria. The cumulative evidence shows extensive oligodendrocytes cell death during the first week post-injury (pi). OPCs and peripheral invading Schwann cells are the dominant cells contributing in myelin formation. The maximum OPC proliferation was observed at around 2 weeks pi and oligodendrogliogenesis continues at later stages until the number of oligodendrocytes return to normal tissue by one month pi. Taken together, the evidence in animals reveals the potential role for endogenous myelinating cells in the axon ensheathment/remyelination after TSCI and this can be the target of pharmacotherapy to induce oligodendrocyte differentiation and myelin formation post-injury

The fate of neurons after traumatic spinal cord injury in rats: a systematic review

Objective(s): To reach an evidence-based knowledge in the context of the temporal-spatial pattern of neuronal death and find appropriate time of intervention in order to preserve spared neurons and promote regeneration after traumatic spinal cord injury (TSCI). Materials and Methods: The study design was based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-guided systematic review. PubMed and EMBASE were searched (24 October, 2015) with no temporal or linguistic restrictions. Hand-search was performed in the bibliographies of relevant articles. Non-interventional animal studies evaluating time-dependent neuronal death following acute mechanical trauma to the spinal cord were included. We separately evaluated the fate of various populations of neurons including propriospinal neurons, ventral motor neurons, Clarke’s column neurons, and supraspinal neurons. Results: We found 11,557 non-duplicated studies. Screening through the titles and abstracts led to 549 articles, 49 of which met the inclusion criteria. Both necrotic and apoptotic neuronal deaths occur after TSCI, though necrosis is the prominent mechanism. There are differences in the responses of intrinsic neurons of the spinal cord to the TSCI. Also, the extent of neuronal death in the supraspinal neurons depends on the anatomical location of their axons. Conclusion: In order to develop new therapies, selection of the injury model and time of intervention has a crucial role in the efficacy of therapy. In addition, examining the safety and efficacy of an intervention by reliable methods not confounded by the injury-related changes would promote translation of therapies to the clinical application

Fabrication and Characterization of Methylprednisolone-Loaded Polylactic Acid/Hyaluronic Acid Nanofibrous Scaffold for Soft Tissue Engineering

Previous in vitro and in vivo studies have indicated that tissue engineering scaffolds, including Schwann cells, may improve axonal regeneration, particularly in combination with Methylprednisolone as an influential neuroprotective factor. The primary aim of this study was to design composite electrospun scaffolds based on polylactic acid (PLA)/ hyaluronic acid (HA) containing various percentages (0.05–2% (w/v)) of Methylprednisolone (MP) with suitable mechanical and chemical properties for soft tissue especially to promote nerve growth. For the first time, MP was implicated in a PLA/HA nanofibrous and its effect on fiber’s properties was scrutinized as a candidate for nerve tissue

Volume Changes After Traumatic Spinal Cord Injury in Animal Studies - A Systematic Review

There are limited data on the lesion volume changes following spinal cord injury (SCI). In this study, a meta-analysis was performed to evaluate the volume size changes of the injured spinal cord over time among animal studies in traumatic SCI. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive electronic search of English literature of PubMed and EMBASE databases from 1946 to 2015 concerning the time-dependent changes in the volume of the spinal cord following mechanical traumatic SCI. A hand-search was also performed for non-interventional, non-molecular, and non-review studies. Quality appraisal, data extraction, qualitative and quantitative analyses were performed afterward. Of 11,561 articles yielded from electronic search, 49 articles were assessed for eligibility after reviewing of titles, abstracts, and references. Ultimately, 11 articles were eligible for quantitative synthesis. The ratio of lesion volume to spinal cord total volume increased over time. Avascularity appeared in spinal cord 4 hours after injury. During the first week, the spinal subarachnoid space decreased. The hemorrhagic lesion size peaked in 1 week and decreased thereafter. Significant loss of gray and white matter occurred from day 3 with a slower progression of white matter damage. Changes of lesion extent over time is critical in pathophysiologic processes after SCI. Early avascularity, rapid loss of gray matter, slow progression of white matter damage, and late cavitation are the pathophysiologic key points of SCI, which could be helpful in choosing the proper intervention on a timely basis

Efficacy of hydrogels for repair of traumatic spinal cord injuries:A systematic review and meta-analysis

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 &lt;.00001) compared to other injury models. The pre-formed implanted hydrogels (SMD: 1.79; 95% CI: 1.24, 2.34; P &lt;.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.</p

Optimization of electrospinning parameters for producing silk fibroin/poly(ethylene oxide) nanofibers using D-optimal method

Despite the ease of the electrospinning process of synthetic polymers, the adjustment of several independent variables for natural ones is a complex procedure. In this work, the electrospinning parameters of silk fibroin (SF)/poly(ethylene oxide) (PEO) blends including tip-to-collector distance (X1), applied voltage (X2), flow rate (X3) and SF/PEO ratio (X4) were optimized using the D-optimal method. By considering the response surface plots and interaction graphs as well as observing the scanning electron microscopy (SEM) images, the optimized conditions were set as follows: X1 = 15 cm, X2 = 12 kV, X3 = 1.2 mL/h and X4 = 4. Accordingly, the electrospun SF/PEO nanofibrous sample with uniform morphology and an average diameter of 182 ± 55 nm was obtained

Early response of Solanum nigrum L. to Lumax and castor oil combination in relation to antioxidant activity, osmolyte concentration and chlorophyll a fluorescence

Abstract Solanum nigrum L. (Black nightshade), is one of the most troublesome weeds of summer crops such as corn, soybean, sunflower, etc. To study the effect of combined Castor oil as an adjuvant with different doses of Lumax (Mesotrion + S-metolacholor + Terbuthylazine) on the physiological behavior of Solanum nigrum L., a greenhouse experiment was conducted in randomized complete block design with four replications in agricultural faculty of the University of Tabriz in 2021. A foliar application of Lumax increased proline, malondialdehyde, and hydrogen peroxide concentrations and superoxide dismutase, catalase, and peroxidase activity. The content of protein and photosynthetic pigments (Chlorophyll a, b, and carotenoids) also decreased significantly by using Lumax herbicide. Applying castor oil in combination with Lumax intensifies oxidative stress and lipid peroxidation. Results showed that by increasing the herbicide doses in comparison with control (non-herbicide), Area, Fm, Fv, Fv/Fm, Fv/F0, Sm, Sm/Tfm, and Fv/F0 decreased 48.32%, 19.52%, 27.95%, 10.47%, 50.90%, 28.34%, 79.38%, and 50.90%, respectively and F0, F0/Fm increased 46.76% and 82.38%, respectively. Castor oil showed a synergistic effect on Lumax herbicide and enhanced its efficacy on Solanum nigrum. The presented results supported the view that by evaluating chlorophyll a fluorescence parameters, we would realize herbicide (alone or mixed with any adjacent) efficacy before the visual symptoms appear in the plant

Improving motor neuron-like cell differentiation of hEnSCs by the combination of epothilone B loaded PCL microspheres in optimized 3D collagen hydrogel

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