Changzhe Wu

Oscillating field stimulation promotes spinal cord remyelination by inducing differentiation of oligodendrocyte precursor cells after spinal cord injury

Demyelination is part of the cascading secondary injury after the primary insult and contributes to the loss of function after spinal cord injury (SCI). Oligodendrocyte precursor cells (OPCs) are the main remyelinating cells in the central nervous system (CNS). We explored whether oscillating field stimulation (OFS) could efficiently promote OPC differentiation and improve remyelination after SCI. SD rats with SCI induced by the Allen method were randomly divided into two groups, the SCI+OFS group and SCI group. The former group received active stimulator units and the latter group received sham (inoperative) stimulator units. Additionally, rats that only received laminectomy were referred as the sham group. The electric field intensity was 600 μV/mm, and the polarity was alternated every 15 minutes. The results showed that the SCI+OFS rats had significantly less demyelination and better locomotor function recovery after 12-weeks treatment. The OFS treatment significantly increased the number of Gal C-positive OPCs after 2-weeks treatment. Furthermore, these rats had higher protein expression of oligodendroglial transcription factors Olig2 and NKx2.2. These findings suggest OFS can promote locomotor recovery and remyelination in SCI rats and this effect may be related to the improved differentiation of OPCs in the spinal cord.

Early applied electric field stimulation attenuates secondary apoptotic responses and exerts neuroprotective effects in acute spinal cord injury of rats.

Injury potential, which refers to a direct current voltage between intact and injured nerve ends, is mainly caused by injury-induced Ca2+ influx. Our previous studies revealed that injury potential increased with the onset and severity of spinal cord injury (SCI), and an application of applied electric field stimulation (EFS) with the cathode distal to the lesion could delay and attenuate injury potential formation. As Ca2+ influx is also considered as a major trigger for secondary injury after SCI, we hypothesize that EFS would protect an injured spinal cord from secondary injury and consequently improve functional and pathological outcomes. In this study, rats were divided into three groups: (1) sham group, laminectomy only; (2) control group, subjected to SCI only; and (3) EFS group, received EFS immediately post-injury with the injury potential modulated to 0±0.5 mV by EFS. Functional recovery of the hind limbs was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. Results revealed that EFS-treated rats exhibited significantly better locomotor function recovery. Luxol fast blue staining was performed to assess the spared myelin area. Immunofluorescence was used to observe the number of myelinated nerve fibers. Ultrastructural analysis was performed to evaluate the size of myelinated nerve fibers. Findings showed that the EFS group rats exhibited significantly less myelin loss and had larger and more myelinated nerve fibers than the control group rats in dorsal corticospinal tract (dCST) 8 weeks after SCI. Furthermore, we found that EFS inhibited the activation of calpain and caspase-3, as well as the expression of Bax, as detected by Western blot analysis. Moreover, EFS decreased cellular apoptosis, as measured by TUNEL, within 4 weeks post-injury. Results suggest that early EFS could significantly reduce spinal cord degeneration and improve functional and historical recovery. Furthermore, these neuroprotective effects may be related to the inhibition of secondary apoptotic responses after SCI. These findings support further investigation of the future clinical application of EFS after SCI.

Electrical stimulation modulates injury potentials in rats after spinal cord injury.

An injury potential is the direct current potential difference between the site of spinal cord injury and the healthy nerves. Its initial amplitude is a significant indicator of the severity of spinal cord injury, and many cations, such as sodium and calcium, account for the major portion of injury potentials. This injury potential, as well as injury current, can be modulated by direct current field stimulation; however, the appropriate parameters of the electrical field are hard to define. In this paper, injury potential is used as a parameter to adjust the intensity of electrical stimulation. Injury potential could be modulated to slightly above 0 mV (as the anode-centered group) by placing the anodes at the site of the injured spinal cord and the cathodes at the rostral and caudal sections, or around –70 mV, which is resting membrane potential (as the cathode-centered group) by reversing the polarity of electrodes in the anode-centered group. In addition, rats receiving no electrical stimulation were used as the control group. Results showed that the absolute value of the injury potentials acquired after 30 minutes of electrical stimulation was higher than the control group rats and much lower than the initial absolute value, whether the anodes or the cathodes were placed at the site of injury. This phenomenon illustrates that by changing the polarity of the electrical field, electrical stimulation can effectively modulate the injury potentials in rats after spinal cord injury. This is also beneficial for the spontaneous repair of the cell membrane and the reduction of cation influx.

A bioelectrical impedance phase angle measuring system for assessment of nutritional status

Bioelectrical impedance phase angle has been recommended as a tool to assess nutrition state, but there are no measuring devices have been specially designed for hospital residents. In this study, a system was established for the measurement of bioelectrical impedance phase angle. The electrical composition, calculation method and measuring method of this system are presented in this paper. Experiments showed excellent performance of this system in measuring impedance made of resistors and capacitors. The designed system was also used to measure the bioelectrical impedance phase angle of both healthy subjects and patients with malnutrition, and the results demonstrated that the phase angle of patients with malnutrition is lower than that of healthy subjects (P < 0.01 for male and P < 0.05 for female). These results suggest that phase angle has the potential to be a useful tool for the quantitative assessment of nutritional status.

Compensation for injury potential by electrical stimulation after acute spinal cord injury in rat

Injury potential, a direct current potential difference between normal section and the site of injury, is a significant index of spinal cord injury. However, its importance has been ignored in the studies of spinal cord electrophysiology and electrical stimulation (ES). In this paper, compensation for injury potential is used as a criterion to adjust the intensity of stimulation. Injury potential is modulated to slightly larger than 0 mV for 15, 30 and 45 minutes immediately after injury by placing the anodes at the site of injury and the cathodes at the rostral and caudal section. Injury potentials of all rats were recorded for statistical analysis. Results show that the injury potentials acquired after ES are higher than those measured from rats without stimulation and much lower than the initial amplitude. It is also observed that the stimulating voltage to keep injury potential be 0 remain the same. This phenomenon suggests that repair of membrane might occur during the period of stimulation. It is also suggested that a constant voltage stimulation can be applied to compensate for injury potential.

Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord

It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG.

Early electrical field stimulation prevents the loss of spinal cord anterior horn motoneurons and muscle atrophy following spinal cord injury

Our previous study revealed that early application of electrical field stimulation (EFS) with the anode at the lesion and the cathode distal to the lesion reduced injury potential, inhibited secondary injury and was neuroprotective in the dorsal corticospinal tract after spinal cord injury (SCI). The objective of this study was to further evaluate the effect of EFS on protection of anterior horn motoneurons and their target musculature after SCI and its mechanism. Rats were randomized into three equal groups. The EFS group received EFS for 30 minutes immediately after injury at T10. SCI group rats were only subjected to SCI and sham group rats were only subjected to laminectomy. Luxol fast blue staining demonstrated that spinal cord tissue in the injury center was better protected; cross-sectional area and perimeter of injured tissue were significantly smaller in the EFS group than in the SCI group. Immunofluorescence and transmission electron microscopy showed that the number of spinal cord anterior horn motoneurons was greater and the number of abnormal neurons reduced in the EFS group compared with the SCI group. Wet weight and cross-sectional area of vastus lateralis muscles were smaller in the SCI group to in the sham group. However, EFS improved muscle atrophy and behavioral examination showed that EFS significantly increased the angle in the inclined plane test and Tarlov’s motor grading score. The above results confirm that early EFS can effectively impede spinal cord anterior horn motoneuron loss, promote motor function recovery and reduce muscle atrophy in rats after SCI.

Electric field stimulation protects injured spinal cord from secondary inflammatory response in rats

Objectives: To investigate acute beneficial effects of electrical field stimulation (EFS) on secondary inflammatory response in spinal cord injury (SCI) rats.OBJECTIVES To investigate acute beneficial effects of electrical field stimulation (EFS) on secondary inflammatory response in spinal cord injury (SCI) rats. METHODS Sprague-Dawley (SD) rats were divided into three groups,sham group rats received laminectomy only, control group rats were subjected to SCI only, and EFS group rats received EFS immediately after the injury. During the 30-min-stimulation, the injury potential modulated to 0 ± 0.5 mV by EFS. At 12h, 24h and 48h after the surgery, the rats in each group were sacrificed. Immunofluorescence staining for macrophage marker (ED-1), the tautomerase activity of macrophage inhibitory factor (MIF) assay and real-time PCR analysis for interleukin-1β (IL-1β) and matrix metalloproteinase-9 (MMP-9) were performed. RESULTS Compared to the rats in control group, the rats treated with EFS presented less ED-1 positive cells 12h (P <; 0.05), 24h (P <; 0.01) and 48h (P <; 0.05) after the surgery and showed a lower MIF tautomerase activity 12h (P <; 0.01), 24h (P <; 0.01) and 48h (P <; 0.01) after the surgery. Moreover, EFS significantly decreased the mRNA levels of IL-β (P <; 0.05) and MMP-9 at 48h (P <; 0.01) after the injury. CONCLUSIONS EFS could attenuate secondary inflammatory response of injured spinal cord shortly after SCI, and EFS treatment could be a candidate for SCI therapy.

Oscillating field stimulation promotes recovery after spinal cord injury in rats: Assessment using behavioral, electrophysiological and histological evaluations.

OBJECTIVES We explored whether oscillating field stimulation (OFS) could efficiently promote motor function recovery in rat model of spinal cord injury. METHODS SD rats with spinal cord injury induced by Allen method was divided into two groups, experimental group rats received active stimulator units and control group rats received sham (inoperative) stimulator units. The electric field intensity was 600μV/mm, and the polarity alternated every 15 min. RESULTS The results showed that the experimental group rats had significantly better locomotor function recovery (inclined-plane testing and modified Tarlov motor grading scale) 5 weeks after the injury (P<;0.05). OFS treatment significantly decreased motor evoked potential (MEP) latency differences and amplitude differences 4 w and 8 w post injury (P<;0.05, P<;0.01). Furthermore, the number of axons was quantified by immunofluorescence staining of nerve fiber (NF), increased axon numbers were observed at 4 w and 8 w in experimental group (P<;0.05). CONCLUSIONS These findings suggest OFS can promote motor function recovery in SCI rats, and this effect may be related to the improving axon regeneration in spinal cord.Objectives: We explored whether oscillating field stimulation (OFS) could efficiently promote motor function recovery in rat model of spinal cord injury. Methods: SD rats with spinal cord injury induced by Allen method was divided into two groups, experimental group rats received active stimulator units and control group rats received sham (inoperative) stimulator units. The electric field intensity was 600μV/mm, and the polarity alternated every 15 min. Results: The results showed that the experimental group rats had significantly better locomotor function recovery (inclined-plane testing and modified Tarlov motor grading scale) 5 weeks after the injury (P<;0.05). OFS treatment significantly decreased motor evoked potential (MEP) latency differences and amplitude differences 4 w and 8 w post injury (P<;0.05, P<;0.01). Furthermore, the number of axons was quantified by immunofluorescence staining of nerve fiber (NF), increased axon numbers were observed at 4 w and 8 w in experimental group (P<;0.05). Conclusions: These findings suggest OFS can promote motor function recovery in SCI rats, and this effect may be related to the improving axon regeneration in spinal cord.

Design of site-directed magnetic targeting system in acute spinal cord injury.

Effective repair immediately after spinal cord injury can improve the prognosis of the patient. Injection of membrane resealing nanomaterial is one of the most promising technique to repair the membrane. In order to improve the retention rate of membrane repair material at injury site, membrane resealing nanomaterial can be combined with magnetic nanoparticle and magnetic targeting system. In this paper, a special site directed magnetic targeting system, which contain a C-shaped permanent magnet and a ferromagnetic needle, was constructed. Simulation was conducted to analyze the influence of the shape of needle on the magnetic field to provide magnetic force large enough to make the magnetic particles stay at the target site. Results showed that the appearance of ferromagnetic needle raised both the strength and the gradient of magnetic field at the target site. Moreover, with similar apex angles, longer needles with larger diameters can produced lager magnetic field, but smaller needles has better focal area at the small injury site in spinal cord injury. These results provide a basis for design and fabrication of ferromagnetic needles when the targeting system is applied in future experiments.Effective repair immediately after spinal cord injury can improve the prognosis of the patient. Injection of membrane resealing nanomaterial is one of the most promising technique to repair the membrane. In order to improve the retention rate of membrane repair material at injury site, membrane resealing nanomaterial can be combined with magnetic nanoparticle and magnetic targeting system. In this paper, a special site directed magnetic targeting system, which contain a C-shaped permanent magnet and a ferromagnetic needle, was constructed. Simulation was conducted to analyze the influence of the shape of needle on the magnetic field to provide magnetic force large enough to make the magnetic particles stay at the target site. Results showed that the appearance of ferromagnetic needle raised both the strength and the gradient of magnetic field at the target site. Moreover, with similar apex angles, longer needles with larger diameters can produced lager magnetic field, but smaller needles has better focal area at the small injury site in spinal cord injury. These results provide a basis for design and fabrication of ferromagnetic needles when the targeting system is applied in future experiments.