Transforaminal Epidural Steroid Injection for Lumbosacral Radiculopathy: Preganglionic versus Conventional Approach

OBJECTIVE: The present study was undertaken to evaluate the effectiveness of transforaminal epidural steroid injection (TFESI) with using a preganglionic approach for treating lumbar radiculopathy when the nerve root compression was located at the level of the supra-adjacent intervertebral disc. MATERIALS AND METHODS: The medical records of the patients who received conventional TFESI at our department from June 2003 to May 2004 were retrospectively reviewed. TFESI was performed in a total of 13 cases at the level of the exiting nerve root, in which the nerve root compression was at the level of the supra-adjacent intervertebral disc (the conventional TFESI group). Since June 2004, we have performed TFESI with using a preganglionic approach at the level of the supra-adjacent intervertebral disc (for example, at the neural foramen of L4-5 for the L5 nerve root) if the nerve root compression was at the level of the supra-adjacent intervertebral disc. Using the inclusion criteria described above, 20 of these patients were also consecutively enrolled in our study (the preganglionic TFESI group). The treatment outcome was assessed using a 5-point patient satisfaction scale and by using a VAS (visual assessment scale). A successful outcome required a patient satisfaction scale score of 3 (very good) or 4 (excellent), and a reduction on the VAS score of > 50% two weeks after performing TFESI. Logistic regression analysis was also performed. RESULTS: Of the 13 patients in the conventional TFESI group, nine showed satisfactory improvement two weeks after TFESI (69.2%). However, in the preganglionic TFESI group, 18 of the 20 patients (90%) showed satisfactory improvement. The difference between the two approaches in terms of TFESI effectiveness was of borderline significance (p = 0.056; odds ratio: 10.483). CONCLUSION: We conclude that preganglionic TFESI has the better therapeutic effect on radiculopathy caused by nerve root compression at the level of the supra-adjacent disc than does conventional TFESI, and the difference between the two treatments had borderline statistical significance

Role of Stem Cell-Derived Exosomes and microRNAs in Spinal Cord Injury

Neurological disorders represent a global health problem. Current pharmacological treatments often lead to short-term symptomatic relief but have dose-dependent side effects, such as inducing orthostatic arterial hypotension due to the blockade of alpha receptors, cardiotoxic effects due to impaired repolarization, and atrioventricular block and tachycardia, including ventricular fibrillation. These challenges have driven the medical community to seek effective treatments for this serious global health threat. Mesenchymal stem cells (MSCs) are pluripotent cells with anti-inflammatory, anti-apoptotic, and immunomodulatory properties, providing a promising alternative due to their ability to differentiate, favorable culture conditions, in vitro manipulation ability, and robust properties. Although MSCs themselves rarely differentiate into neurons at the site of injury after transplantation in vivo, paracrine factors secreted by MSCs can create environmental conditions for cell-to-cell communication and have shown therapeutic effects. Recent studies have shown that the pleiotropic effects of MSCs, particularly their immunomodulatory potential, can be attributed primarily to these paracrine factors. Exosomes derived from MSCs are known to play an important role in these effects. Many studies have evaluated the potential of exosome-based therapies for the treatment of various neurological diseases. In addition to exosomes, various miRNAs derived from MSCs have been identified to regulate genes and alleviate neuropathological changes in neurodegenerative diseases. This review explores the burgeoning field of exosome-based therapies, focusing on the effects of MSC-derived exosomes and exosomal miRNAs, and summarizes recent findings that shed light on the potential of exosomes in the treatment of neurological disorders. The insights gained from this review may pave the way for innovative and effective treatments for these complex conditions. Furthermore, we suggest the therapeutic effects of exosomes and exosomal miRNAs from MSCs, which have a rescue potential in spinal cord injury via diverse signaling pathways

Endoplasmic Reticulum Stress Causing Apoptosis in a Mouse Model of an Ischemic Spinal Cord Injury

A spinal cord injury (SCI) is the devastating trauma associated with functional deterioration due to apoptosis. Most laboratory SCI models are generated by a direct impact on an animal’s spinal cord; however, our model does not involve the direct impact on the spinal cord. Instead, we use a clamp compression to create an ischemia in the descending aortas of mice. Following the success of inducing an ischemic SCI (ISCI), we hypothesized that this model may show apoptosis via an endoplasmic reticulum (ER) stress pathway. This apoptosis by the ER stress pathway is enhanced by the inducible nitric oxide synthase (iNOS). The ER is used for the protein folding in the cell. When the protein folding capacity is overloaded, the condition is termed the ER stress and is characterized by the accumulation of misfolded proteins inside the ER lumen. The unfolded protein response (UPR) signaling pathways that deal with the ER stress response then become activated. This UPR activates the three signal pathways that are regulated by the inositol-requiring enzyme 1α (IRE1α), the activating transcription factor 6 (ATF6), and the protein kinase RNA-like ER kinase (PERK). IRE1α and PERK are associated with the expression of the apoptotic proteins. Apoptosis caused by an ISCI is assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. An ISCI also reduces synaptophysin and the neuronal nuclear protein (NeuN) in the spinal cord. In conclusion, an ISCI increases the ER stress proteins, resulting in apoptosis in neuronal cells in the spinal cord

Mass Production of Early-Stage Bone-Marrow-Derived Mesenchymal Stem Cells of Rat Using Gelatin-Coated Matrix

Although preparation of early-stage bone-marrow-derived mesenchymal stem cells (BM-MSCs) is critical for successful cell transplantation therapy, no culture system offers a sufficient number of early-stage BM-MSCs for cell transplantation. Accordingly, we developed a culture system capable of producing a large number of early-stage BM-MSCs by using gelatin-coated matrix. The greatest retrieval and proliferation rates of the earliest-stage rat BM-MSCs were detected in bone-marrow-derived cells cultured on 1% (wt/v) gelatin-coated matrix, which showed significantly greater colony forming unit-fibroblast number, diameter, and total cell number. Moreover, continuous culture of the earliest-stage BM-MSCs on 1% (wt/v) gelatin-coated matrix resulted in a maximum of 21.2±2.7 fold increase in the cumulative total number of early-stage BM-MSCs at passage 5. BM-MSCs generated in large quantities due to a reduced doubling time and an increased yield of cell population in S/G2/M phase showed typical fibroblast-like morphology and no significant differences in BM-MSC-related surface marker expression and differentiation potential, except for an increased ratio of differentiation into a neurogenic lineage. The use of gelatin-coated matrix in the retrieval and culture of BM-MSCs contributes greatly to the effective isolation and mass production of early-stage BM-MSCs