Study on neural stem cells and spinal cord injury: Based on bibliometric analysis

Dear Sir, We read the important paper of Shamim et al.[5] about the question as to whether patients with spinal cord injury (SCI) benefit from spinal stabilization. We believe that the decision to perform spine surgery on patents with SCI should not be made only based on duration of hospital stay, economic issues, and neurological outcome.[4] However, we would emphasize the apparent advantage of non-operative management of SCI patients in developing countries. In Zahedan, a city located in a poor socioeconomic province of Iran, we managed 108 patients with SCI during a 12-year period from 1994 to 2005. Of these patients, 50 were followed for more than 12 months. Assessment of outcome of these patients not only confirmed superiority of non-surgical management in patients with complete SCI in terms of cost and duration of hospitalization, but also, surprisingly, showed that the neurological outcome of patients with incomplete SCI in the non-surgical group was not different from that of the surgical group. Length of stay in surgery group of SCI patients was 11.1 ± 5.46 days, which was significantly longer than 5.8 ± 0.96 days in non-surgical patients (P = 0.017). All groups of patients with incomplete SCI including those treated non-operatively, patients had early operation or cases underwent late surgery, had significant and similar improvement, when compared to the preoperative examination (P = 0.02), with no difference among these three groups.[2,3] Our results differ from those of the meta-analysis of La Rosa et al.,[1] which concluded neurological improvement after early decompression in incomplete SCI patients compared to late decompression or non-surgical management. In this meta-analysis, 26 studies were evaluated, all of which had been performed in developed countries, with no study from developing countries. The results of this meta-analysis is also different from the study performed by Shamim et al.,[5] which may indicate different outcome of spinal cord decompression in developed and developing countries. Despite the limitations of the study by Shamim et al.,[5] such as heterogeneous cohort of patients, inconsistent prednisolone prescription, late decompression in considerable number of patients, different surgical procedures, and lack of post-operative neurologic assessment of patients, it can be hypothesized that the country where surgery is performed (developing vs. developed countries) may have an effect on the outcome of SCI patients. Thus, results of some reports on favorable outcome of patients undergoing spinal decompression/stabilization from developed countries should be interpreted carefully if they are to be used in developing countries since many pre-, intra- and post-operative factors may contribute to the outcome of these patients. Further studies from developing countries should be performed to provide better guidance for spine surgeons in these countries to decide whether an SCI patient is likely to benefit from spinal decompression/stabilization or not.

Benefiting from in-depth research into stem cells, extracellular vesicles (EVs), which are byproducts of cells and membrane-wrapped microvesicles (30-120 nm) containing lipids, proteins, and nucleic acids, may cast light on the research and development of therapeutics capable of improving the neurological recovery of spinal cord injury (SCI) animals. However, the mechanistic modes of action for EVs in alleviating the lesion size of SCI remain to be solved, thus presenting a tremendous gap existing in translation from the laboratory to the clinic. The purpose of this minireview was to cover a wide range of basic views on EVs involved in SCI treatment, including the effects of EVs on the pathogenesis, treatment, and diagnosis of spinal cord injury. We searched databases (i.e., PubMed, Web of Science, Scopus, Medline, and EMBASE) and acquired all accessible articles published in the English language within five years. Studies reporting laboratory applications of EVs in the treatment of SCI were included and screened to include studies presenting relevant molecular mechanisms. This review first summarized the basic role of EVs in cell communication, cell death, inflammatory cascades, scar formation, neuronal regrowth, and angiogenesis after SCI, thereby providing insights into neuroprotection and consolidated theories for future clinical application of EVs. EVs participate in an extremely wide range of cell activities, play a critical role in cell communication centring neurons, and are considered potential therapies and biomarkers for SCI. miRNAs are the most abundant nucleic acids shipped by EVs and effluent cytokines, and they may represent important messengers of EVs and important factors in SCI treatment.

Is Sleep Disordered Breathing Confounding Rehabilitation Outcomes in Spinal Cord Injury Research?

Purpose – The paper aims at analyzing literature available on the topic water conservation using bibliometric analysis. The purpose is to explore important information such as publication growth, citation trends, prominent sources, most contributing countries, frequent keywords, apex organizations, and to figure out existing co-authorships in the field. Design / Methodology / Approach – For conducting Bibliometric analysis, 395 articles published in English language, are extracted from Web of Science (WoS) database for a decade specifically from 2015 to 2024. The analysis is done by using two softwares namely, Biblioshiny in R studio (version 4.4.1) and VOSviewer (version 1.6.20). Findings – The study highlights a significant growth in number of publications, along with some decline in citation trend. ‘Sustainability’ and ‘Water’ are found to be the pertinent journals in the field. Further, China is the most contributing country in terms of publications and citations received. Also, the apex affiliation in terms of number of publications is from China specifically from ‘China University of Mining and Technology’. Moreover, Management, Water, Impact, Model, Performance, Climate-Change, Conservation, Systems, Soil, and Irrigation are highlighted as the trendy keywords of the decade. Originality / Value – In this bibliometric analysis, water conservation has been linked to the solution and answer keywords. However in prior literature, bibliometric analysis on water conservation has not been performed using this kind of viewpoint. Hence, the analysis becomes significant due to this paper’s unique findings. Keywords – Water Conservation, Bibliometric Analysis, Sustainable Development Goals (SDGs), Web of Science (WoS), Biblioshiny, VOSviewer. Paper Type – Literature Review

Chitosan nanoparticles and valproic acid are demonstrated as the protective agents in the treatment of spinal cord injury (SCI). However, the effects of valproic acid-labeled chitosan nanoparticles (VA-CN) on endogenous spinal cord neural stem cells (NSCs) following SCI and the underlying mechanisms involved remain to be elucidated. In this study, the VA-CN was constructed and the effects of VA-CN on NSCs were assessed in a rat model of SCI. We found VA-CN treatment promoted recovery of the tissue and locomotive function following SCI. Moreover, administration of VA-CN significantly enhanced neural stem cell proliferation and the expression levels of neurotrophic factors following SCI. Furthermore, administration of VA-CN led to a decrease in the number of microglia following SCI. In addition, VA-CN treatment significantly increased the Tuj 1- positive cells in the spinal cord of the SCI rats, suggesting that VA-CN could enhance the differentiation of NSCs following SCI. In conclusion, these results demonstrated that VA-CN could improve the functional and histological recovery through promoting the proliferation and differentiation of NSCs following SCI, which would provide a newly potential therapeutic manner for the treatment of SCI.

Telemedicine and digital management in repair and regeneration after nerve injury and in nervous system diseases.

Objectives: The aim of this study was to conduct a bibliometric analysis of the literature on stem cell treatment for spinal cord injury to gain an intuitive understanding of how the field is progressing, discover topics of interest, and determine what development trends are emerging in this field.Background: Spinal cord injury and its complications often cause an enormous economic burden, and postinjury repair and treatment have always been challenging in clinical and scientific research. Stem cell therapy for spinal cord injury can prevent immune rejection and induce the release of neuroprotective and anti-inflammatory factors to reduce the production of stress-related proteins, reactive oxygen species, and inflammatory reactions.Methods: We analyzed the number and quality of publications in the field of stem cell therapy in spinal cord injury between 2018.01.01 and 2023.06.30 in the core collection database of Web of Science. CiteSpace and VOSviewer were used to sort and summarize these studies by country, institution, authors' publications, and collaborative networks. In addition, the research topics of interest were identified and summarized.Results: This study ultimately included 2,150 valid papers, with the number of publications showing a gradual upward trend. The country, institution, author and journal with the greatest number of publications and citations are China, the Chinese Academy of Sciences, Dai JW, and the International Journal of Molecular Sciences, respectively. The top three high-frequency keyword clusters were hereditary paraplegia, reactive astrocytes and tissue engineering.Conclusion: With the help of visual analysis, we identified general trends and research topics of interest in the field of spinal cord injury over the last 5 years. Our findings suggest that stem cell transplantation for spinal cord injury and exosome therapy may be a focus of future research. This study provides a foundation for future research on stem cell therapy as well as clinical efforts in this field.

Neuronal cell-specific gene expression system and neural stem cells (NSCs) were combined for treatment of spinal cord injury (SCI). To verify the reproducibility of the neuronal cell-specific therapeutic gene overexpression system, we develop a neuronal cell-specific granulocyte-macrophage colony-stimulating factor expression system (NSE-GMCSF), and then examine the characteristics of GMCSF overexpression and protective effect on neural cells in vitro and vivo. The stem cell transplantation is considered a promising therapy for SCI. However, stem cell monotherapy strategy is insufficient for complete recovery after SCI. Therefore, combined treatment method based on stem cells with other therapeutic system may be effective for improving the therapeutic efficacy. In this study, we established the gene and stem cell therapy platform based on NSCs and neuronal cell-specific gene expression system. To examine the GMCSF expression pattern, we compared the amount of secreted GMCSF from the neuronal cell-specific GMCSF expressing NSCs with control GMCSF-expressing NSCs (respectively, NSE-GMCSF-NSCs vs. SV-GMCSF-NSCs) by ELISA in vitro and in vivo, and then verified the neuronal protective effect of these cells in vitro and vivo. The results showed that NSE-GMCSF-NSCs secreted more GMCSF compared with SV-GMCSF-NSCs in normoxia, hypoxia and cytotoxic conditions. The cell viability of NSE-GMCSF-NSCs was increased depending on the amount of secreted GMCSF in cytotoxic condition. In addition, the amount of secreted GMCSF by NSE-GMCSF-NSCs transplanted into injured spinal cord was significantly higher than SV-GMCSF-NSCs. Higher amount of secreted GMCSF decreased the expression of proapoptotic protein, Bax. In this study, we demonstrated that the neuronal cell-specific gene expression system induced overexpression of GMCSF in NSCs. These combined NSCs & gene therapy treatment protocol would be an effective therapeutic system for SCI. N/A.

Objective To repair the injured spinal cord in adult rats using tissue-engineered neural complex constructed in vitro by tissue engineering techniques and discuss the treatment effect.Methods Neural stem cells (NSCs) from rats were cultured separately and modified collagen scaffold was also prepared to construct complex of NSCs /modified collagen scaffold in vitro.Embryo spine cord extract was administered to induce differentiation of NSCs,the structure of which was revealed by histochemical technique and scanning electron microscope.The rat models of hemisected spinal cord injury were built and grafted with tissue-engineered neural complex.Functional recovery of the models was evaluated every two weeks postoperatively.Effect in repair of spinal cord injury was assessed by histological method at postoperative three and eight weeks.Results After tissue-engineered neural complex planted in the modified collagen scaffold was grafted into the injured spinal cord in adult rats,the seed cells survived and further differentiated into functionally active neurons.The differentiated glia cells presented quite regular reticular structure.Motor function below the level of the injured spinal cord in adult rats obtained obvious recovery.Conclusion Tissue-engineered neural complex seeded in the modified collagen scaffold takes effect in structural reconstruction and functional recovery of the injured spinal cord in adult rats. Key words: Spinal cord injuries; Tissue engineering; Neural stem cells; Collagen

Spinal cord injury is a severe central nervous system disorder, burdening patients and society. Current treatments, such as early surgeries and corticosteroid therapy, have limited efficacy and potential risks. Moreover, rehabilitation training only offers partial recovery. This review aims to summarize the latest advances in preclinical and clinical research on cutting-edge treatment technologies for spinal cord injury, including neuromodulation, pharmacological strategies, cell therapies, surgical interventions, tissue engineering, and rehabilitation training. Neuromodulation such as brain-computer interfaces restores motor function by decoding neural signals, while epidural spinal cord stimulation combined with rehabilitation training notably enhances motor and autonomic nervous function. In terms of cell therapy, co-transplantation of mesenchymal stem cells and Schwann cells promotes neural repair, while genetically engineered neural progenitor cells enhance regenerative potential through directed differentiation. In addition, the combination of tissue engineering scaffolds and biomaterials offers new ways to repair the neural microenvironment, and hypothalamus-targeted deep brain stimulation markedly improves walking ability in patients with chronic spinal cord injury. Current spinal cord injury treatments are shifting from a single-modality approach to multimodal integration, such as combining neural stimulation with stem cell transplantation and optimizing cell functions through gene editing technologies. Further research is needed to unravel the complex pathological mechanisms of spinal cord injury, advance personalized therapies, and develop artificial intelligence-assisted rehabilitation technologies, ultimately guiding precise neural functional reconstruction and long-term recovery. Multidisciplinary collaboration and technological innovation will be the key to overcoming the current bottlenecks in the treatment of spinal cord injury.

This study presents a novel partial differential equation (PDE)-based model for neural stem cell (NSC) therapy in spinal cord injury (SCI) treatment. Existing models often fail to accurately represent NSC migration, differentiation, and interaction with biomaterials and immune responses. By integrating scaffold-mediated diffusion and immune response dynamics, the proposed model offers a more realistic framework for regenerative therapy optimization. The model improves upon previous approaches by providing precise control overgrowth factor distribution, ensuring sustained bioavailability for enhanced NSC survival and functional integration. Applications of this framework extend beyond SCI treatment, with potential implications for neurodegenerative diseases, brain injury repair, and personalized medicine. Future research will focus on experimental validation and machine learning-driven optimization to refine the predictive capabilities of the model.

Transplantation of neural stem cells (NSCs) holds great potential for the treatment of spinal cord injury (SCI). However, transplanted NSCs poorly survive in the SCI environment. We injected NSCs into tibial nerve and transplanted tibial nerve into a hemisected spinal cord and investigated the effects of lithium chloride (LiCl) on the survival of spinal neurons, axonal regeneration, and functional recovery. Our results show that most of the transplanted NSCs expressed glial fibrillary acidic protein, while there was no obvious expression of nestin, neuronal nuclei, or acetyltransferase found in NSCs. LiCl treatment produced less macrosialin (ED1) expression and axonal degeneration in tibial nerve after NSC injection. Our results also show that a regimen of LiCl treatment promoted NSC differentiation into NF200-positive neurons with neurite extension into the host spinal cord. The combination of tibial nerve transplantation with NSCs and LiCl injection resulted in more host motoneurons surviving in the spinal cord, more regenerated axons in tibial nerve, less glial scar area, and decreased ED1 expression. We conclude that lithium may have therapeutic potential in cell replacement strategies for central nervous system injury due to its ability to promote survival and neuronal generation of grafted NSCs and reduced host immune reaction.

Spinal cord injury is a debilitating condition that often results in permanent impairments in motor, sensory, and autonomic functions. The potential for treating spinal cord injury with ultrasound is increasingly being recognized. Ultrasound addresses several key aspects of spinal cord injury, including promoting nerve healing by creating a regenerative environment, attenuating inflammation, and managing secondary complications. While preclinical studies show encouraging results, further translational efforts are necessary to adapt these therapies for clinical use. Insights gained from transcranial ultrasound applications, such as transducer selection, anatomical considerations, and pre-treatment planning, can provide valuable guidance for optimizing ultrasound treatments for spinal cord injury. This literature review highlights the exciting potential of ultrasound therapy in spinal cord injury research and the importance of refining treatment parameters and strategies for successful clinical translation.

There is no effective strategy for the treatment of spinal cord injury (SCI), a devastating condition characterized by severe hypoxia and ischemic insults. In this study, we investigated the histology and pathophysiology of the SCI milieu in a rat model and found that areas of hypoxia were unevenly interspersed in compressed SCI. With this new knowledge, we generated embryonic neural stem cells (NSCs) expressing basic fibroblast growth factor (bFGF) under the regulation of five hypoxia‐responsive elements (5HRE) using a lentiviral vector (LV‐5HRE‐bFGF‐NSCs) to specifically target these hypoxic loci. SCI models treated with bFGF expressed by the LV‐5HRE‐bFGF‐NSCs viral vector demonstrated improved recovery, increased neuronal survival, and inhibited autophagy in spinal cord lesions in the rat model due to the reversal of hypoxic conditions at day 42 after injury. Furthermore, improved functional restoration of SCI with neuron regeneration was achieved in vivo, accompanied by glial scar inhibition and the evidence of axon regeneration across the scar boundary. This is the first study to illustrate the presence of hypoxic clusters throughout the injury site of compressed SCI and the first to show that the transplantation of LV‐5HRE‐bFGF‐NSCs to target this hypoxic microenvironment enhanced the recovery of neurological function after SCI in rats; LV‐5HRE‐bFGF‐NSCs may therefore be a good candidate to evaluate cellular SCI therapy in humans.

The purpose of this study was to evaluate the risk factors for spinal cord injury (SCI) in patients with acute aortic dissection undergoing surgery with frozen elephant trunk technique (FET). From December 2014 to February 2018, 17 patients with acute aortic dissection underwent surgical treatment of the aortic arch with FET. SCI occurred in 3 patients. Risk factors for SCI were evaluated. Mean age of the patients was 56years and 88.2% were male. The ratio of true lumen to total aortic diameter at the level of carina (before: 0.48 vs. after: 0.75, P < 0.001), aortic valve (before: 0.47 vs. after: 0.67, P = 0.001), and celiac artery (before: 0.48 vs. after: 0.68, P = 0.003) increased after surgery. There were no significant differences in perioperative minimum hemoglobin level and postoperative mean arterial pressure between patients with and without SCI. However, patients with SCI had higher creatinine level before surgery (SCI: 1.32mg/dL vs. no SCI: 0.81mg/dL, P = 0.023). Although there was no difference in number of patent intercostal arteries before surgery, those originating from the true lumen were fewer in patients with SCI (SCI: 2.7 vs. no SCI: 8.6, P = 0.021). Furthermore, with entry closure, significant decrease in patency was observed in intercostal arteries originating from the false lumen (before: 3.1 vs. after: 1.0, P < 0.001). FET was useful in entry closure. However, FET in patients with higher creatinine level and those who may have significant spinal cord perfusion from the false lumen could be a risk factor for postoperative SCI.