RESUMEN
Background: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms. Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs' projections and evaluate neurotransmitters' expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn. Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters' expression in anterior horn of lumbar spinal cord. Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters' expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit.
Asunto(s)
Nanopartículas Magnéticas de Óxido de Hierro , Traumatismos de la Médula Espinal , Animales , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/fisiopatología , Nanopartículas Magnéticas de Óxido de Hierro/química , Ratones , Locomoción/fisiología , Recuperación de la Función/fisiología , Médula Espinal , Condicionamiento Físico Animal , Formación Reticular , Magnetoterapia/métodos , Ratones Endogámicos C57BL , Femenino , Potenciales Evocados Motores/fisiologíaRESUMEN
BACKGROUND: Upper limb dysfunction after stroke seriously affects quality of life. Bilateral training has proven helpful in recovery of upper limb motor function in these patients. However, studies evaluating the effectiveness of bilateral upper limb robot-assisted training on improving motor function and quality of life in stroke patients are lacking. Quantitative electroencephalography (EEG) is non-invasive, simple, and monitors cerebral cortical activity, which can be used to evaluate the effectiveness of interventions. In this study, EEG was used to evaluate the effect of end-drive bilateral upper extremity robot-assisted training on upper extremity functional recovery in stroke patients. METHODS: 24 stroke patients with hemiplegia were randomly divided into a conventional training (CT, n = 12) group or a bilateral upper limb robot-assisted training (BRT, n = 12) group. All patients received 60 min of routine rehabilitation treatment including rolling, transferring, sitting, standing, walking, etc., per day, 6 days a week, for three consecutive weeks. The BRT group added 30 min of bilateral upper limb robot-assisted training per day, while the CT group added 30 min of upper limb training (routine occupational therapy) per day, 6 days a week, for 3 weeks. The primary outcome index to evaluate upper limb motor function was the Fugl-Meyer functional score upper limb component (FMA-UE), with the secondary outcome of activities of daily living (ADL), assessed by the modified Barthel index (MBI) score. Quantitative EEG was used to evaluate functional brain connectivity as well as alpha and beta power current source densities of the brain. RESULTS: Significant (p < 0.05) within-group differences were found in FMA-UE and MBI scores for both groups after treatment. A between-group comparison indicated the MBI score of the BRT group was significantly different from that of the CT group, whereas the FMA-UE score was not significantly different from that of the CT group after treatment. The differences of FMA-UE and MBI scores before and after treatment in the BRT group were significantly different as compared to the CT group. In addition, beta rhythm power spectrum energy was higher in the BRT group than in the CT group after treatment. Functional connectivity in the BRT group, under alpha and beta rhythms, was significantly increased in both the bilateral frontal and limbic lobes as compared to the CT group. CONCLUSIONS: BRT outperformed CT in improving ADL in stroke patients within three months, and BRT facilitates the recovery of upper limb function by enhancing functional connectivity of the bilateral cerebral hemispheres.
Asunto(s)
Robótica , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Actividades Cotidianas , Calidad de Vida , Resultado del Tratamiento , Extremidad Superior , ElectroencefalografíaRESUMEN
Background: Sarcopenia is an aging-related degeneration of muscle mass and strength. Small-molecule inhibitor SW033291 has been shown to attenuate muscle atrophy. Targeted nanodrug-delivery systems can improve the efficacy of small-molecule inhibitors. Methods: The skeletal muscle cell-targeted nanoparticle was called AP@SW033291, which consisted of SW033291, modular peptide ASSLNIAGGRRRRRG and PEG-DSPE. Nanoparticles were featured with particle size, fluorescence emission spectra and targeting ability. We also investigated their effects on muscle mass and function. Results: The size of AP@SW033291 was 125.7 nm and it demonstrated targeting effects on skeletal muscle; thus, it could improve muscle mass and muscle function. Conclusion: Nanoparticle AP@SW033291 could become a potential strategy to strengthen the treatment effects of small-molecule inhibitors in sarcopenia.
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Nanopartículas , Sarcopenia , Humanos , Sarcopenia/tratamiento farmacológico , Piridinas , Fibras Musculares EsqueléticasRESUMEN
Spasticity commonly emerges during the process of recovery after spinal cord injury (SCI) and critically exacerbates motor dysfunction. Given insufficient effects of individual therapies, we combined repetitive transcranial magnetic stimulation (rTMS) with treadmill training (Tr) in rats with SCI to investigate potential synergistic effects on alleviating spasticity and motor dysfunction. Animals were randomized into four groups: SCI only, rTMS, Tr, and rTMS plus Tr. At the study endpoint eight weeks after the start of interventions, the rTMS plus Tr group exhibited the largest decrease in maximal H-reflex amplitude/maximal M-wave amplitude ratio (effect size (ES): -0.082, 95% confidence interval (CI): -0.118 to -0.046, p < 0.001) as well as the greatest improvement in motor function measured with the Basso, Beattie, and Bresnahan locomotor scale (ES: 1.811, 95% CI: 1.018 to 2.603, p < 0.001; significantly different from all other groups at p < 0.01) and grid-walking test (ES: -5.1, 95% CI: -7.784 to -2.416, p < 0.001, significantly different from rTMS alone at p < 0.01). Pathological analyses demonstrated that the combined treatment facilitated the growth of serotonergic axons around the lesion site, and the upregulation of 5-hydroxytryptamine, potassium-chloride cotransporter-2, and glutamic acid decarboxylases 67 in the lumbar spinal cord distal to the injury site. All effects of combined treatment of rTMS and treadmill training were enhanced compared to treadmill training or rTMS alone. Treadmill training and rTMS intervention appear to have synergistic effects on hyperreflexia and locomotion likely related to a restored balance between facilitatory and inhibitory inputs to motoneurons.
Asunto(s)
Traumatismos de la Médula Espinal , Estimulación Magnética Transcraneal , Animales , Neuronas Motoras/patología , Espasticidad Muscular/terapia , Ratas , Reflejo Anormal , Médula Espinal/patología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/terapiaRESUMEN
BACKGROUND This study aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) and treadmill training (TT) on motor function recovery in rats with partial spinal cord injury (SCI). MATERIAL AND METHODS Sixty rats with moderate partial SCI at the 9th thoracic vertebral level induced by a Louisville Injury System Apparatus impactor were randomly allocated to 5 groups: Sham surgery (Intact); Sham rTMS without TT (S-rTMS/Non-TT); Sham rTMS with TT (S-rTMS/TT); rTMS without TT (rTMS/Non-TT); and rTMS with TT (rTMS/TT). Interventions commenced 8 days after SCI and continued for 8 weeks. Outcomes studied were Basso, Beattie, and Bresnahan locomotor scale scores, grid walking test, and biochemical analysis of the brain-derived neurotrophic factor (BDNF), synapsin I (SYN), and postsynaptic density protein-95 (PSD-95) in the motor cortex and spinal cord. RESULTS The rTMS/TT contributed to greater Basso, Beattie, and Bresnahan scores compared with the S-rTMS/Non-TT (P<0.01), S-rTMS/TT (P<0.05), and rTMS/Non-TT (P<0.05), and showed obviously reduced numbers of foot drops compared with the S-rTMS/Non-TT (P<0.05). The rTMS/TT significantly increased the expressions of BDNF, SYN, and PSD-95 compared with the S-rTMS/Non-TT, both in the motor cortex (P<0.01, P<0.01, P<0.001, respectively) and spinal cord (P<0.001, P<0.01, P<0.05, respectively). CONCLUSIONS In a modified rat model of SCI, combined rTMS with TT improved motor function, indicating that this combined approach promoted adaptive neuroplasticity between the motor cortex and the spinal cord. A combined app roach to improving motor function following SCI requires further evaluation to determine the possible clinical applications.