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3.
Front Public Health ; 12: 1377513, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224559

RESUMEN

Objective: To evaluate the leading challenges in developing countries' traumatic spinal cord injury (TSCI) care. Methods: We conducted a systematic search in electronic databases of PubMed, SCOPUS, Web of Science, EMBASE, and Cochrane Library on 16 April 2023. Studies that investigated challenges associated with the management of TSCI in developing countries were eligible for review. We extracted related outcomes and categorized them into four distinct parts: injury prevention, pre-hospital care, in-hospital care, and post-hospital care. Results: We identified 82 articles that met the eligibility criteria including 13 studies on injury prevention, 25 on pre-hospital care, 32 on in-hospital care, and 61 on post-hospital care. Challenges related to post-hospital problems including the personal, financial, and social consequences of patients' disabilities and the deficiencies in empowering people with TSCI were foremost studied. Lack of trained human resources, insufficient public education and delays in care delivery were barriers in the acute and chronic management of TSCI. A well-defined pre-hospital network and standard guidelines for the management of acute neurotrauma are needed. Critical challenges in injury prevention include deficiencies in infrastructure and supportive legislation. Conclusion: Studies focusing on injury prevention and pre-hospital care in TSCI management in developing countries warrant further investigation. It is imperative to develop systematic and evidence-based initiatives that are specifically tailored to the unique circumstances of each country to address these challenges effectively. By understanding the primary obstacles, policymakers and healthcare providers can establish goals for improving education, planning, legislation, and resource allocation.


Asunto(s)
Países en Desarrollo , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/terapia , Humanos , Atención a la Salud
4.
Int J Mol Sci ; 25(17)2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39273538

RESUMEN

Spinal cord injury (SCI) is a catastrophic condition that disrupts neurons within the spinal cord, leading to severe motor and sensory deficits. While current treatments can alleviate pain, they do not promote neural regeneration or functional recovery. Three-dimensional (3D) bioprinting offers promising solutions for SCI repair by enabling the creation of complex neural tissue constructs. This review provides a comprehensive overview of 3D bioprinting techniques, bioinks, and stem cell applications in SCI repair. Additionally, it highlights recent advancements in 3D bioprinted scaffolds, including the integration of conductive materials, the incorporation of bioactive molecules like neurotrophic factors, drugs, and exosomes, and the design of innovative structures such as multi-channel and axial scaffolds. These innovative strategies in 3D bioprinting can offer a comprehensive approach to optimizing the spinal cord microenvironment, advancing SCI repair. This review highlights a comprehensive understanding of the current state of 3D bioprinting in SCI repair, offering insights into future directions in the field of regenerative medicine.


Asunto(s)
Bioimpresión , Impresión Tridimensional , Traumatismos de la Médula Espinal , Ingeniería de Tejidos , Andamios del Tejido , Traumatismos de la Médula Espinal/terapia , Humanos , Bioimpresión/métodos , Andamios del Tejido/química , Animales , Ingeniería de Tejidos/métodos , Medicina Regenerativa/métodos , Regeneración Nerviosa
5.
Cells ; 13(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39273075

RESUMEN

Spinal cord injury (SCI) is a serious condition accompanied by severe adverse events that affect several aspects of the patient's life, such as motor, sensory, and functional impairment. Despite its severe consequences, definitive treatment for these injuries is still missing. Therefore, researchers have focused on developing treatment strategies aimed at ensuring full recovery post-SCI. Accordingly, attention has been drawn toward cellular therapy using mesenchymal stem cells. Considering their wide availability, decreased immunogenicity, wide expansion capacity, and impressive effectiveness in many therapeutic approaches, adipose-derived stem cell (ADSC) injections in SCI cases have been investigated and showed promising results. In this review, SCI pathophysiology and ADSC transplantation benefits are discussed independently, together with SCI animal models and adipose stem cell preparation and application techniques. The mechanisms of healing in an SCI post-ADSC injection, the outcomes of this therapeutic approach, and current clinical trials are also deliberated, in addition to the challenges and future perspectives, aiming to encourage further research in this field.


Asunto(s)
Tejido Adiposo , Traumatismos de la Médula Espinal , Trasplante de Células Madre , Traumatismos de la Médula Espinal/terapia , Humanos , Animales , Tejido Adiposo/citología , Trasplante de Células Madre/métodos , Células Madre/citología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Trasplante de Células Madre Mesenquimatosas/métodos , Modelos Animales de Enfermedad
6.
Int J Mol Sci ; 25(16)2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39201431

RESUMEN

Recent studies have highlighted the therapeutic potential of stem cells for various diseases. However, unlike other tissues, brain tissue has a specific structure, consisting of synapses. These synapses not only transmit but also process and refine information. Therefore, synaptic regeneration plays a key role in therapy of neurodegenerative disorders. Neurexins (NRXNs) and neuroligins (NLGNs) are synaptic cell adhesion molecules that connect pre- and postsynaptic neurons at synapses, mediate trans-synaptic signaling, and shape neural network properties by specifying synaptic functions. In this study, we investigated the synaptic regeneration effect of human neural stem cells (NSCs) overexpressing NRXNs (F3.NRXN) and NLGNs (F3.NLGN) in a spinal cord injury model. Overexpression of NRXNs and NLGNs in the neural stem cells upregulated the expression of synaptophysin, PSD95, VAMP2, and synapsin, which are synaptic markers. The BMS scores indicated that the transplantation of F3.NRXN and F3.NLGN enhanced the recovery of locomotor function in adult rodents following spinal cord injury. Transplanted F3.NRXN and F3.NLGN differentiated into neurons and formed a synapse with the host cells in the spinal cord injury mouse model. In addition, F3.NRXN and F3.NLGN cells restored growth factors (GFs) and neurotrophic factors (NFs) and induced the proliferation of host cells. This study suggested that NSCs overexpressing NRXNs and NLGNs could be candidates for cell therapy in spinal cord injuries by facilitating synaptic regeneration.


Asunto(s)
Moléculas de Adhesión Celular Neuronal , Modelos Animales de Enfermedad , Células-Madre Neurales , Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/genética , Células-Madre Neurales/metabolismo , Animales , Humanos , Moléculas de Adhesión Celular Neuronal/metabolismo , Moléculas de Adhesión Celular Neuronal/genética , Ratones , Sinapsis/metabolismo , Trasplante de Células Madre/métodos , Diferenciación Celular , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Femenino , Neuroliginas
7.
Int J Mol Sci ; 25(16)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39201729

RESUMEN

Traumatic spinal cord injury is a major cause of disability for which there are currently no fully effective treatments. Recent studies using epidural electrical stimulation have shown significant advances in motor rehabilitation, even when applied during chronic phases of the disease. The present study aimed to investigate the effectiveness of epidural electric stimulation in the motor recovery of rats with spinal cord injury. Furthermore, we aimed to elucidate the neurophysiological mechanisms underlying motor recovery. First, we improved upon the impact spinal cord injury model to cause severe and permanent motor deficits lasting up to 2 months. Next, we developed and tested an implantable epidural spinal cord stimulator device for rats containing an electrode and an implantable generator. Finally, we evaluated the efficacy of epidural electrical stimulation on motor recovery after spinal cord injury in Wistar rats. A total of 60 animals were divided into the following groups: (i) severe injury with epidural electrical stimulation (injury + stim, n = 15), (ii) severe injury without stimulation (group injury, n = 15), (iii) sham implantation without battery (sham, n = 15), and (iv) a control group, without surgical intervention (control, n = 15). All animals underwent weekly evaluations using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale index, inclined plane, and OpenField test starting one week before the lesion and continuing for eight weeks. After this period, the animals were sacrificed and their spinal cords were explanted and prepared for histological analysis (hematoxylin-eosin) and immunohistochemistry for NeuN, ß-III-tubulin, synaptophysin, and Caspase 3. Finally, NeuN-positive neuronal nuclei were quantified through stereology; fluorescence signal intensities for ß-tubulin, synaptophyin, and Caspase 3 were quantified using an epifluorescence microscope. The injury + stim group showed significant improvement on the BBB scale compared with the injured group after the 5th week (p < 0.05). Stereological analysis showed a significantly higher average count of neural cells in the injury + stim group in relation to the injury group (1783 ± 2 vs. 897 ± 3, p < 0.001). Additionally, fluorescence signal intensity for synaptophysin was significantly higher in the injury + stim group in relation to the injury group (1294 ± 46 vs. 1198 ± 23, p < 0.01); no statistically significant difference was found in ß-III-tubulin signal intensity. Finally, Caspase 3 signal intensity was significantly lower in the stim group (727 ± 123) compared with the injury group (1225 ± 87 p < 0.05), approaching levels observed in the sham and control groups. Our data suggest a regenerative and protective effect of epidural electrical stimulation in rats subjected to impact-induced traumatic spinal cord injury.


Asunto(s)
Modelos Animales de Enfermedad , Plasticidad Neuronal , Ratas Wistar , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/patología , Ratas , Recuperación de la Función , Terapia por Estimulación Eléctrica/métodos , Sinaptofisina/metabolismo , Tubulina (Proteína)/metabolismo , Espacio Epidural/patología , Médula Espinal/metabolismo , Médula Espinal/patología , Médula Espinal/fisiopatología , Masculino , Caspasa 3/metabolismo , Regeneración Nerviosa , Femenino , Proteínas del Tejido Nervioso , Antígenos Nucleares
8.
Cells ; 13(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39195214

RESUMEN

Following spinal cord injury (SCI), the regenerative capacity of the central nervous system (CNS) is severely limited by the failure of axonal regeneration. The regeneration of CNS axons has been shown to occur by grafting predegenerated peripheral nerves (PPNs) and to be promoted by the transplantation of neural precursor cells (NPCs). The introduction of a combinatorial treatment of PPNs and NPCs after SCI has to address the additional problem of glial scar formation, which prevents regenerating axons from leaving the implant and making functional connections. Previously, we discovered that the synthetic sulfoglycolipid Tol-51 inhibits astrogliosis. The objective was to evaluate axonal regeneration and locomotor function improvement after SCI in rats treated with a combination of PPN, NPC, and Tol-51. One month after SCI, the scar tissue was removed and replaced with segments of PPN or PPN+Tol-51; PPN+NPC+Tol-51. The transplantation of a PPN segment favors regenerative axonal growth; in combination with Tol-51 and NPC, 30% of the labeled descending corticospinal axons were able to grow through the PPN and penetrate the caudal spinal cord. The animals treated with PPN showed significantly better motor function. Our data demonstrate that PPN implants plus NPC and Tol-51 allow successful axonal regeneration in the CNS.


Asunto(s)
Regeneración Nerviosa , Células-Madre Neurales , Nervios Periféricos , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/patología , Ratas , Regeneración Nerviosa/efectos de los fármacos , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/trasplante , Células-Madre Neurales/citología , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/patología , Femenino , Axones/efectos de los fármacos , Glucolípidos/farmacología , Recuperación de la Función/efectos de los fármacos
9.
Stem Cell Res Ther ; 15(1): 264, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39183334

RESUMEN

OBJECTIVE: Neurological and functional impairments are commonly observed in individuals with spinal cord injury (SCI) due to insufficient regeneration of damaged axons. Exosomes play a crucial role in the paracrine effects of mesenchymal stem cells (MSCs) and have emerged as a promising therapeutic approach for SCI. Thus, this study aimed to evaluate the safety and potential effects of intrathecal administration of allogeneic exosomes derived from human umbilical cord MSCs (HUC-MSCs) in patients with complete subacute SCI. METHODS: This study was a single-arm, open-label, phase I clinical trial with a 12-month follow-up period. HUC-MSCs were extracted from human umbilical cord tissue, and exosomes were isolated via ultracentrifugation. After intrathecal injection, each participant a underwent complete evaluation, including neurological assessment using the American Spinal Injury Association (ASIA) scale, functional assessment using the Spinal Cord Independence Measure (SCIM-III), neurogenic bowel dysfunction (NBD) assessment using the NBD score, modified Ashworth scale (MAS), and lower urinary tract function questionnaire. RESULTS: Nine patients with complete subacute SCI were recruited. The intrathecal injection of allogeneic HUC-MSCs-exosomes was safe and well tolerated. No early or late adverse event (AE) attributable to the study intervention was observed. Significant improvements in ASIA pinprick (P-value = 0.039) and light touch (P-value = 0.038) scores, SCIM III total score (P-value = 0.027), and NBD score (P-value = 0.042) were also observed at 12-month after the injection compared with baseline. CONCLUSIONS: This study demonstrated that intrathecal administration of allogeneic HUC-MSCs-exosomes is safe in patients with subacute SCI. Moreover, it seems that this therapy might be associated with potential clinical and functional improvements in these patients. In this regard, future larger phase II/III clinical trials with adequate power are highly required. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20200502047277N1. Registered 2 October 2020, https://en.irct.ir/trial/48765 .


Asunto(s)
Exosomas , Inyecciones Espinales , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Traumatismos de la Médula Espinal , Cordón Umbilical , Humanos , Traumatismos de la Médula Espinal/terapia , Exosomas/metabolismo , Masculino , Femenino , Adulto , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Persona de Mediana Edad , Trasplante de Células Madre Mesenquimatosas/métodos , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Cordón Umbilical/citología , Trasplante Homólogo/métodos , Adulto Joven
10.
Sci Rep ; 14(1): 18031, 2024 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-39098975

RESUMEN

Spinal cord injury (SCI) is damage or trauma to the spinal cord, which often results in loss of function, sensation, or mobility below the injury site. Transcranial direct current stimulation (tDCS) is a non-invasive and affordable brain stimulation technique used to modulate neuronal circuits, which changes the morphology and activity of microglia in the cerebral cortex. However, whether similar morphological changes can be observed in the spinal cord remains unclear. Therefore, we evaluated neuronal population activity in layer 5 (L5) of M1 following SCI and investigated whether changes in the activities of L5 neurons affect microglia-axon interactions using C57BL/6J mice. We discovered that L5 of the primary motor cortex (corticospinal neurons) exhibited reduced synchronized activity after SCI that correlates with microglial morphology, which was recovered using tDCS. This indicates that tDCS promotes changes in the morphological properties and recovery of microglia after SCI. Combining immunotherapy with tDCS may be effective in treating SCI.


Asunto(s)
Ratones Endogámicos C57BL , Microglía , Corteza Motora , Recuperación de la Función , Traumatismos de la Médula Espinal , Estimulación Transcraneal de Corriente Directa , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Animales , Microglía/metabolismo , Estimulación Transcraneal de Corriente Directa/métodos , Ratones , Corteza Motora/fisiopatología , Modelos Animales de Enfermedad , Masculino , Médula Espinal/fisiopatología , Médula Espinal/patología , Femenino
11.
Spinal Cord Ser Cases ; 10(1): 56, 2024 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-39098854

RESUMEN

INTRODUCTION: Spinal cord injury (SCI) causes damage to neurons and results in motor and sensory dysfunction. Intermittent theta burst stimulation (iTBS) has been used to induce neuronal and synaptic plasticity by applying a magnetic field in the brain. The plasticity induced in the cortex has an imperative role in the recovery of motor and sensory functioning. However, the effect of iTBS in complete SCI patients is still elusive. CASE PRESENTATION: We report here the case of a 27-year-old female who sustained an L1 complete spinal cord injury (SCI) with an ASIA score of A. The patient lost all the sensory and motor functions below the level of injury. Intermittent theta burst stimulation (iTBS) was administered at 80% of the resting motor threshold over the M1 motor cortex, along with intensive rehabilitation training to promote sensorimotor function. DISCUSSION: There was a partial recovery in functional, electrophysiological, and neurological parameters. The case report also demonstrates the safety and efficacy of iTBS in complete SCI patients. No adverse event has been observed in the patient during intervention sessions.


Asunto(s)
Traumatismos de la Médula Espinal , Estimulación Magnética Transcraneal , Humanos , Traumatismos de la Médula Espinal/rehabilitación , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Femenino , Adulto , Estimulación Magnética Transcraneal/métodos , Recuperación de la Función/fisiología , Corteza Motora , Ritmo Teta/fisiología
12.
Explore (NY) ; 20(5): 103037, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39163704

RESUMEN

OBJECTIVE: To explore the effect of the mindfulness-based stress reduction (MBSR) practice on sleep quality and perceived stress in patients with spinal cord injury (SCI). METHOD: A total of 104 patients with SCI (diagnosed via imaging and clinical symptoms) admitted to our hospital between January 2020 and December 2022 were selected as the study participants. The patients were randomly divided into two groups: the MBSR (observation) group and the control group. The observation group received MBSR therapy and routine nursing, and the control group received music training therapy and routine nursing. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and the perceived stress score was used to evaluate stress experienced by the patients at three timepoints: before intervention, 4 weeks and 8weeks after intervention. RESULTS: Compared with before intervention, the PSQI scores of both the control group and intervention group participants significantly decreased after intervention(P < 0.01). Compared with the 4 weeks after intervention, the PSQI scores of both groups of participants decreased in the 8 weeks after intervention(P < 0.01). There was a significant difference in PSQI scores between the two groups of participants at 4 and 8 weeks after intervention(P < 0.01). Compared with before intervention, the average perceived stress score of both the control group and intervention group participants significantly decreased after intervention(P < 0.05). Compared with the 4 weeks after intervention, the average perceived stress score of both groups of participants decreased in the 8 weeks after intervention(P < 0.01). There was a significant difference in average perceived stress score between the two groups of participants at 4(P < 0.05) and 8 weeks(P < 0.01) after intervention(P < 0.01). CONCLUSION: The use of MBSR therapy could effectively improve patient sleep quality and reduce perceived stress.


Asunto(s)
Atención Plena , Calidad del Sueño , Traumatismos de la Médula Espinal , Estrés Psicológico , Humanos , Atención Plena/métodos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/psicología , Traumatismos de la Médula Espinal/terapia , Femenino , Masculino , Estrés Psicológico/terapia , Adulto , Persona de Mediana Edad , Musicoterapia/métodos
13.
J Med Case Rep ; 18(1): 386, 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39152447

RESUMEN

BACKGROUND: Experimental studies have shown that repetitive trans-spinal magnetic stimulation (TsMS) decreases demyelination and enables recovery after spinal cord injury (SCI). However, the usefulness of TsMS in humans with SCI remains unclear. Therefore, the main objective of this study is to evaluate the effects of TsMS combined with kinesiotherapy on SCI symptoms. We describe a protocol treatment with TsMS and kinesiotherapy in a patient with SCI due to neuromyelitis optica (NMO)-associated transverse myelitis. CASE PRESENTATION: A 23-year-old white male with NMO spectrum disorders started symptoms in 2014 and included lumbar pain evolving into a mild loss of strength and sensitivity in both lower limbs. Five months later, the symptoms improved spontaneously, and there were no sensorimotor deficits. Two years later, in 2016, the symptoms recurred with a total loss of strength and sensitivity in both lower limbs. Initially, physiotherapy was provided in 15 sessions with goals of motor-sensory recovery and improving balance and functional mobility. Subsequently, TsMS (10 Hz, 600 pulses, 20-seconds inter-trains interval, at 90% of resting motor threshold of the paravertebral muscle) was applied at the 10th thoracic vertebral spinous process before physiotherapy in 12 sessions. Outcomes were assessed at three time points: prior to physiotherapy alone (T-1), before the first session of TsMS combined with kinesiotherapy (T0), and after 12 sessions of TsMS combined with kinesiotherapy (T1). The patient showed a 25% improvement in walking independence, a 125% improvement in balance, and an 18.8% improvement in functional mobility. The Patient Global Impression of Change Scale assessed the patient's global impression of change as 'much improved'. CONCLUSION: TsMS combined with kinesiotherapy may safely and effectively improve balance, walking independence, and functional mobility of patients with SCI due to NMO-associated transverse myelitis.


Asunto(s)
Magnetoterapia , Neuromielitis Óptica , Recuperación de la Función , Traumatismos de la Médula Espinal , Humanos , Masculino , Neuromielitis Óptica/terapia , Neuromielitis Óptica/complicaciones , Adulto Joven , Magnetoterapia/métodos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Traumatismos de la Médula Espinal/terapia , Resultado del Tratamiento , Terapia Combinada , Modalidades de Fisioterapia
14.
Spinal Cord Ser Cases ; 10(1): 64, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39174519

RESUMEN

STUDY DESIGN: A feasibility pilot study. OBJECTIVE: To assess the feasibility a full-scale Randomized Controlled Trial aimed at assessing the beneficial effect of a Virtual Walking (VW)-based (Experimental intervention (EI)) on neuropathic pain and functionality in people with incomplete spinal cord injury (SCI). SETTING: A hospital service (Hospital Universitario y Politécnico La Fe) and disability associations (TetraSport, CODIFIVA and ASPAYM). METHODS: Twelve people with chronic incomplete SCI were randomized to EI (VW plus therapeutic exercise program (TE)) -or Control Intervention (CI (placebo VW and TE)) groups. A six-week intervention (3 sessions/week) was carried out. To assess feasibility, the following outcomes were used: level of restriction and validity of inclusion and exclusion criteria, participants' compliance, accessibility and acceptability of the intervention for participants, adequate pre-training time of physiotherapists. To explore therapy effectiveness, pain severity, and interference, mean and maximum isometric strength, walking speed, and walking ability were assessed before (Time 1, T1) and after (Time 2, T2) the intervention. RESULTS: 20% of the participants initially recruited did not meet inclusion criteria. In addition, all participants completed at least 80% of the intervention sessions and none of the participants dropped out before T2. No serious adverse event was found. Moreover, 91.67% of participants were willing to perform the intervention again and all therapists involved were adequately pre-trained. Finally, our preliminary results suggest that the proposed EI is effective. CONCLUSION: A full-scale RCT is feasible and preliminary results suggest that VW with TE could have a beneficial impact on pain and functionality in this population.


Asunto(s)
Terapia por Ejercicio , Estudios de Factibilidad , Traumatismos de la Médula Espinal , Caminata , Humanos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Traumatismos de la Médula Espinal/terapia , Masculino , Femenino , Persona de Mediana Edad , Terapia por Ejercicio/métodos , Adulto , Caminata/fisiología , Proyectos Piloto , Resultado del Tratamiento , Neuralgia/terapia , Neuralgia/etiología , Anciano
15.
Turk Neurosurg ; 34(5): 888-897, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39087298

RESUMEN

AIM: To assess the effect of intravenously injected superparamagnetic iron oxide nanoparticle (SPION)-labeled adipose-derived stem cells (ADSCs) under an external magnetic field on the efficacy of ADSC transplantation in rats with spinal cord injury (SCI). MATERIAL AND METHODS: ADSCs were isolated from rats, labeled with SPIONs, and divided into magnetic and non-magnetic groups. A rat model of SCI was established, and SCI rats were randomly divided into magnetic, non-magnetic, and control groups, with ten rats in each group. Rats in the magnetic and non-magnetic groups were injected with SPION-labeled ADSCs via the tail vein. A 300-mT neodymium iron boron magnet was placed externally at the SCI site of the rats in the magnetic group. One and two weeks after successful modeling, SCI rats were scored for the degree of SCI followed by histopathology of the spinal cord, number of ADSCs at the SCI site, and growth-associated protein-43 (GAP-43) expression were determined in the spinal cord tissues. RESULTS: One and two weeks after modeling, the Basso-beattie bresnahan (BBB) scores were the highest in the magnetic group, followed by the non-magnetic group, and the lowest in the control group. HE staining showed that the histopathological manifestations of the spinal cord in the magnetic group were somewhat improved compared to those in the non-magnetic and control groups. Two weeks after modeling, Prussian blue staining revealed that the number of ADSCs was significantly higher in the spinal cord tissue of the magnetic group than in that of the non-magnetic group. One and two weeks after modeling, western blotting revealed that the magnetic group exhibited the highest GAP-43 expression. CONCLUSION: An external magnetic field applied at the SCI site in rats exerted a directional effect on SPION-labeled ADSCs, directing their migration and improving the efficacy of stem cell-targeted therapies for SCI.


Asunto(s)
Campos Magnéticos , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/terapia , Ratas , Ratas Sprague-Dawley , Nanopartículas Magnéticas de Óxido de Hierro , Trasplante de Células Madre/métodos , Masculino , Modelos Animales de Enfermedad , Tejido Adiposo/citología , Médula Espinal , Células Madre , Proteína GAP-43/metabolismo , Nanopartículas de Magnetita
16.
J Transl Med ; 22(1): 724, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39103885

RESUMEN

BACKGROUND: The traumatic spinal cord injury (SCI) can cause immediate multi-faceted function loss or paralysis. Microglia, as one of tissue resident macrophages, has been reported to play a critical role in regulating inflammation response during SCI processes. And transplantation with M2 microglia into SCI mice promotes recovery of motor function. However, the M2 microglia can be easily re-educated and changed their phenotype due to the stimuli of tissue microenvironment. This study aimed to find a way to maintain the function of M2 microglia, which could exert an anti-inflammatory and pro-repair role, and further promote the repair of spinal cord injury. METHODS: To establish a standard murine spinal cord clip compression model using Dumont tying forceps. Using FACS, to sort microglia from C57BL/6 mice or CX3CR1GFP mice, and further culture them in vitro with different macrophage polarized medium. Also, to isolate primary microglia using density gradient centrifugation with the neonatal mice. To transfect miR-145a-5p into M2 microglia by Lipofectamine2000, and inject miR-145a-5p modified M2 microglia into the lesion sites of spinal cord for cell transplanted therapy. To evaluate the recovery of motor function in SCI mice through behavior analysis, immunofluorescence or histochemistry staining, Western blot and qRT-PCR detection. Application of reporter assay and molecular biology experiments to reveal the mechanism of miR-145a-5p modified M2 microglia therapy on SCI mice. RESULTS: With in vitro experiments, we found that miR-145a-5p was highly expressed in M2 microglia, and miR-145a-5p overexpression could suppress M1 while promote M2 microglia polarization. And then delivery of miR-145a-5p overexpressed M2 microglia into the injured spinal cord area significantly accelerated locomotive recovery as well as prevented glia scar formation and neuron damage in mice, which was even better than M2 microglia transplantation. Further mechanisms showed that overexpressed miR-145a-5p in microglia inhibited the inflammatory response and maintained M2 macrophage phenotype by targeting TLR4/NF-κB signaling. CONCLUSIONS: These findings indicate that transplantation of miR-145a-5p modified M2 microglia has more therapeutic potential for SCI than M2 microglia transplantation from epigenetic perspective.


Asunto(s)
Ratones Endogámicos C57BL , MicroARNs , Microglía , Recuperación de la Función , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/patología , MicroARNs/metabolismo , MicroARNs/genética , Microglía/metabolismo , Ratones
17.
J Neurosci Methods ; 411: 110267, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39191303

RESUMEN

BACKGROUND: This study investigates the potential of transcranial magnetic stimulation (TMS) to enhance spinal cord axon regeneration by modulating corticospinal pathways and improving motor nerve function recovery in rats with spinal cord injury (SCI). NEW METHOD: TMS is a non-invasive neuromodulation technique that generates a magnetic field to activate neurons in the brain, leading to depolarization and modulation of cortical activity. Initially utilized for brain physiology research, TMS has evolved into a diagnostic and prognostic tool in clinical settings, with increasing interest in its therapeutic applications. However, its potential for treating motor dysfunction in SCI has been underexplored. RESULTS: The TMS intervention group exhibited significant improvements compared to the control group across behavioral assessments, neurophysiological measurements, pathological analysis, and immunological markers. COMPARISON WITH EXISTING METHODS: Unlike most studies that focus on localized spinal cord injury or muscle treatments, this study leverages the non-invasive, painless, and highly penetrating nature of TMS to focus on the corticospinal tracts, exploring its therapeutic potential for SCI. CONCLUSIONS: TMS enhances motor function recovery in rats with SCI by restoring corticospinal pathway integrity and promoting axonal regeneration. These findings highlight TMS as a promising therapeutic option for SCI patients with currently limited treatment alternatives.


Asunto(s)
Regeneración Nerviosa , Tractos Piramidales , Ratas Sprague-Dawley , Recuperación de la Función , Traumatismos de la Médula Espinal , Estimulación Magnética Transcraneal , Animales , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Estimulación Magnética Transcraneal/métodos , Tractos Piramidales/fisiopatología , Tractos Piramidales/fisiología , Femenino , Regeneración Nerviosa/fisiología , Recuperación de la Función/fisiología , Modelos Animales de Enfermedad , Axones/fisiología , Ratas , Potenciales Evocados Motores/fisiología
18.
Eur J Pharmacol ; 982: 176950, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39214270

RESUMEN

Spinal cord injury (SCI) is a serious and disabling injury that is often accompanied by neuropathic pain (NeP), which severely affects patients' motor and sensory functions and reduces their quality of life. Currently, there is no specific treatment for treating SCI and relieving the accompanying pain, and we can only rely on medication and physical rehabilitation, both of which are ineffective. Researchers have recently identified a novel class of glial cells, olfactory ensheathing cells (OECs), which originate from the olfactory system. Transplantation of OECs into damaged spinal cords has demonstrated their capacity to repair damaged nerves, improve the microenvironment at the point of injury, and They can also restore neural connectivity and alleviate the patient's NeP to a certain extent. Although the effectiveness of OECs transplantation has been confirmed in experiments, the specific mechanisms by which it repairs the spinal cord and relieves pain have not been articulated. Through a review of the literature, it has been established that the ability of OECs to repair and relieve pain is inextricably linked to its anti-inflammatory and immunomodulatory effects. In this regard, it is imperative to gain a deeper understanding of how OECs exert their anti-inflammatory and immunomodulatory effects. The objective of this paper is to provide a comprehensive overview of the mechanisms by which OECs exert anti-inflammatory and immunomodulatory effects. We aim to manipulate the immune microenvironment at the transplantation site through the intervention of cytokines and immune cells, with the goal of enhancing OECs' function or creating a conducive microenvironment for OECs' survival. This approach is expected to improve the therapeutic efficacy of OECs in clinical settings. However, numerous fundamental and clinical challenges remain to be addressed if OEC transplantation therapy is to become a standardized treatment in clinical practice.


Asunto(s)
Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/complicaciones , Humanos , Animales , Neuralgia/terapia , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Trasplante de Células/métodos , Bulbo Olfatorio/citología , Neuroglía/trasplante
19.
Am J Emerg Med ; 84: 50-55, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39089143

RESUMEN

OBJECTIVE: To determine frequency that ED visits are needed, and the most common chief complaints and medications prescribed to Veterans with spinal cord injuries and disorders (SCI/D). METHODS: The Veterans Health Administration (VHA) SCI and Disorders (SCI/D) Registry (VHA SCIDR) was used to identify Veterans with SCI/D over a five-year period (fiscal years 2018-2022). The primary outcome was the proportion of Veterans with SCI/D who had visits to the ED during the study period. Secondary outcomes included diagnostic codes and medications prescribed in the ED, and other healthcare encounters. RESULTS: Overall, 18,464 Veterans with SCI/D, including 80,661 patient-years were included. Of these Veterans, 10,234 (55.4%) had at least one ED visit and 8230 (44.6%) did not. ED visits were consistent, ranging from 33.5% to 36.4% annually. The number of in-person healthcare encounters decreased over the study period. The most common ED diagnostic codes were paraplegia or quadriplegia, discharge counseling, UTI, neuromuscular dysfunction of the bladder and low back pain. The most common medications prescribed in the ED were analgesics (e.g., acetaminophen, ketorolac), antimicrobials (e.g., ceftriaxone, vancomycin) and ondansetron. Antibiotics were among the most prescribed discharge medications, including ciprofloxacin, sulfamethoxazole/trimethoprim, cephalexin, and doxycycline. CONCLUSION: This national study of Veterans with SCI/D characterized ED healthcare utilization. Overall, more than half of Veterans with SCI/D required an ED visit during the five-year study period and over one third of Veterans in each fiscal year required an ED visit. Interventions to target prevention of ED visits and subsequent hospitalizations could focus on these areas.


Asunto(s)
Servicio de Urgencia en Hospital , Traumatismos de la Médula Espinal , Veteranos , Humanos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Masculino , Femenino , Estados Unidos/epidemiología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/terapia , Veteranos/estadística & datos numéricos , Persona de Mediana Edad , Adulto , United States Department of Veterans Affairs/estadística & datos numéricos , Sistema de Registros , Anciano , Enfermedades de la Médula Espinal
20.
Int J Biol Macromol ; 277(Pt 4): 134591, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39127289

RESUMEN

Spinal cord injury (SCI) is a debilitating condition that can result in significant functional impairment and loss of quality of life. There is a growing interest in developing new therapies for SCI, and hydrogel-based multimodal therapeutic strategies have emerged as a promising approach. They offer several advantages for SCI repair, including biocompatibility, tunable mechanical properties, low immunogenicity, and the ability to deliver therapeutic agents. This article provides an overview of the recent advances in hydrogel-based therapy strategies for SCI repair, particularly within the past three years. We summarize the SCI hydrogels with varied characteristics such as phase-change hydrogels, self-healing hydrogel, oriented fibers hydrogel, and self-assembled microspheres hydrogel, as well as different functional hydrogels such as conductive hydrogels, stimuli-responsive hydrogels, adhesive hydrogel, antioxidant hydrogel, sustained-release hydrogel, etc. The composition, preparation, and therapeutic effect of these hydrogels are briefly discussed and comprehensively evaluated. In the end, the future development of hydrogels in SCI repair is prospected to inspire more researchers to invest in this promising field.


Asunto(s)
Hidrogeles , Traumatismos de la Médula Espinal , Cicatrización de Heridas , Hidrogeles/administración & dosificación , Hidrogeles/química , Animales , Traumatismos de la Médula Espinal/terapia , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química
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