[Research on the brain phantom for transcranial electromagnetic neuromodulation].

Transcranial magnetic stimulation (TMS), a widely used neuroregulatory technique, has been proven to be effective in treating neurological and psychiatric disorders. The therapeutic effect is closely related to the intracranial electric field caused by TMS, thus accurate measurement of the intracranial electric field generated by TMS is of great significance. However, direct intracranial measurement in human brain faces various technical, safety, ethical and other limitations. Therefore, we have constructed a brain phantom that can simulate the electrical conductivity and anatomical structure of the real brain, in order to replace the clinical trial to achieve intracranial electric field measurement. We selected and prepared suitable conductive materials based on the electrical conductivity of various layers of the real brain tissue, and performed image segmentation, three-dimensional reconstruction and three-dimensional printing processes on each layer of tissue based on magnetic resonance images. The production of each layer of tissue in the brain phantom was completed, and each layer of tissue was combined to form a complete brain phantom. The induced electric field generated by the TMS coil applied to the brain phantom was measured to further verify the conductivity of the brain phantom. Our study provides an effective experimental tool for studying the distribution of intracranial electric fields caused by TMS.

[Research progress on transcranial electrical stimulation for deep brain stimulation].

Transcranial electric stimulation (TES) is a non-invasive, economical, and well-tolerated neuromodulation technique. However, traditional TES is a whole-brain stimulation with a small current, which cannot satisfy the need for effectively focused stimulation of deep brain areas in clinical treatment. With the deepening of the clinical application of TES, researchers have constantly investigated new methods for deeper, more intense, and more focused stimulation, especially multi-electrode stimulation represented by high-precision TES and temporal interference stimulation. This paper reviews the stimulation optimization schemes of TES in recent years and further analyzes the characteristics and limitations of existing stimulation methods, aiming to provide a reference for related clinical applications and guide the following research on TES. In addition, this paper proposes the viewpoint of the development direction of TES, especially the direction of optimizing TES for deep brain stimulation, aiming to provide new ideas for subsequent research and application.

[The influence of tissue conductivity on the calculation of electric field in the transcranial magnetic stimulation head model].

In transcranial magnetic stimulation (TMS), the conductivity of brain tissue is obtained by using diffusion tensor imaging (DTI) data processing. However, the specific impact of different processing methods on the induced electric field in the tissue has not been thoroughly studied. In this paper, we first used magnetic resonance image (MRI) data to create a three-dimensional head model, and then estimated the conductivity of gray matter (GM) and white matter (WM) using four conductivity models, namely scalar (SC), direct mapping (DM), volume normalization (VN) and average conductivity (MC), respectively. Isotropic empirical conductivity values were used for the conductivity of other tissues such as the scalp, skull, and cerebrospinal fluid (CSF), and then the TMS simulations were performed when the coil was parallel and perpendicular to the gyrus of the target. When the coil was perpendicular to the gyrus where the target was located, it was easy to get the maximum electric field in the head model. The maximum electric field in the DM model was 45.66% higher than that in the SC model. The results showed that the conductivity component along the electric field direction of which conductivity model was smaller in TMS, the induced electric field in the corresponding domain corresponding to the conductivity model was larger. This study has guiding significance for TMS precise stimulation.

[Study on deep brain magnetic stimulation method based on magnetic replicator].

Existing neuroregulatory techniques can achieve precise stimulation of the whole brain or cortex, but high-focus deep brain stimulation has been a technical bottleneck in this field. In this paper, based on the theory of negative permeability emerged in recent years, a simulation model of magnetic replicator is established to study the distribution of the induced electric field in the deep brain and explore the possibility of deep focusing, which is compared with the traditional magnetic stimulation method. Simulation results show that a single magnetic replicator realized remote magnetic source. Under the condition of the same position and compared with the traditional method of stimulating, the former generated smaller induced electric field which sharply reduced with distance. By superposition of the magnetic field replicator, the induced electric field intensity could be increased and the focus could be improved, reducing the number of peripheral wires while guaranteeing good focus. The magnetic replicator model established in this paper provides a new idea for precise deep brain stimulation, which can be combined with neuroregulatory techniques in the future to lay a foundation for clinical application.

[Experimental study of electric field stimulation combined with polyethylene glycol in the treatment of spinal cord injury in rats].

Electric field stimulation (EFS) can effectively inhibit local Ca 2+ influx and secondary injury after spinal cord injury (SCI). However, after the EFS, the Ca 2+ in the injured spinal cord restarts and subsequent biochemical reactions are stimulated, which affect the long-term effect of EFS. Polyethylene glycol (PEG) is a hydrophilic polymer material that can promote cell membrane fusion and repair damaged cell membranes. This article aims to study the combined effects of EFS and PEG on the treatment of SCI. Sprague-Dawley (SD) rats were subjected to SCI and then divided into control group (no treatment, n = 10), EFS group (EFS for 30 min, n = 10), PEG group (covered with 50% PEG gelatin sponge for 5 min, n = 10) and combination group (combined treatment of EFS and PEG, n = 10). The measurement of motor evoked potential (MEP), the motor behavior score and spinal cord section fast blue staining were performed at different times after SCI. Eight weeks after the operation, the results showed that the latency difference of MEP, the amplitude difference of MEP and the ratio of cavity area of spinal cords in the combination group were significantly lower than those of the control group, EFS group and PEG group. The motor function score and the ratio of residual nerve tissue area in the spinal cords of the combination group were significantly higher than those in the control group, EFS group and PEG group. The results suggest that the combined treatment can reduce the pathological damage and promote the recovery of motor function in rats after SCI, and the therapeutic effects are significantly better than those of EFS and PEG alone.

Oscillating field stimulation promotes axon regeneration and locomotor recovery after spinal cord injury.

Oscillating field stimulation (OFS) is a potential method for treating spinal cord injury. Although it has been used in spinal cord injury (SCI) therapy in basic and clinical studies, its underlying mechanism and the correlation between its duration and nerve injury repair remain poorly understood. In this study, we established rat models of spinal cord contusion at T10 and then administered 12 weeks of OFS. The results revealed that effectively promotes the recovery of motor function required continuous OFS for more than 6 weeks. The underlying mechanism may be related to the effects of OFS on promoting axon regeneration, inhibiting astrocyte proliferation, and improving the linear arrangement of astrocytes. This study was approved by the Animal Experiments and Experimental Animal Welfare Committee of Capital Medical University (supplemental approval No. AEEI-2021-204) on July 26, 2021.

Effects of the combination therapy of electric field stimulation and polyethylene glycol in the ex vivo spinal cord of female rats after compression.

The application of electric field stimulation (EFS) can reduce the cation influx after spinal cord injury. However, regenerated cation influx and reestablished injury potential are observed after EFS. Polyethylene glycol (PEG) is popular as an effective cell membrane fusion agent. This study aims to determine the effects of the combination therapy of EFS and PEG in the ex vivo spinal cord after compression. The ex vivo spinal cords of female rats with compression injury were incubated in a double sucrose gap recording chamber (DSGRC) and randomly divided into the following four groups: (1) compression group: compression only, (2) EFS group: EFS for 15 min, (3) PEG group: PEG treatment for 4 min, and (4) EFS + PEG group: EFS for 15 min and PEG treatment for 4 min. The hematoxylin-eosin staining was performed to measure the necrotic area of the spinal cords. The gap potential was detected, and the area under the curve of the gap potential was calculated. The intracellular cation concentration, membrane permeability, and compound action potential were measured and quantified. Results revealed no significant difference in the necrotic areas among different groups, and the compression model of the ex vivo spinal cord in the DSGRC had high consistency and stability. The combination therapy could attenuate cation inflow, promote cell membrane restoration, and promote the functional recovery of the spinal cord conduction after compression in ex vivo spinal cords.

[Simulation study of spinal cord stimulation evoked compound action potential].

Spinal cord stimulation (SCS) for pain is usually implanted as an open loop system using unchanged parameters. To avoid the under and over stimulation caused by lead migration, evoked compound action potentials (ECAP) is used as feedback signal to change the stimulating parameters. This study established a simulation model of ECAP recording to investigate the relationship between ECAP component and dorsal column (DC) fiber recruitment. Finite element model of SCS and multi-compartment model of sensory fiber were coupled to calculate the single fiber action potential (SFAP) caused by single fiber in different spinal cord regions. The synthetized ECAP, superimposition of SFAP, could be considered as an index of DC fiber excitation degree, because the position of crests and amplitude of ECAP corresponds to different fiber diameters. When 10% or less DC fibers were excited, the crests corresponded to fibers with large diameters. When 20% or more DC fibers were excited, ECAP showed a slow conduction crest, which corresponded to fibers with small diameters. The amplitude of this slow conduction crest increased as the stimulating intensity increased while the amplitude of the fast conduction crest almost remained unchanged. Therefore, the simulated ECAP signal in this paper could be used to evaluate the degree of excitation of DC fibers. This SCS-ECAP model may provide theoretical basis for future clinical application of close loop SCS base on ECAP.

[Electric field simulation and analysis of modified electroconvulsive therapy and magnetic seizure therapy in a realistic human head model].

Modified electroconvulsive therapy (MECT) and magnetic seizure therapy (MST) are effective treatments for severe major depression. MECT has better efficacy in the treatment than MST, but it has cognitive and memorial side effects while MST does not. To study the causes of these different outcomes, this study contrasted the electric filed strength and spatial distribution induced by MECT and MST in a realistic human head model. Electric field strength induced by MECT and MST are simulated by the finite element method, which was based on a realistic human head model obtained by magnetic resonance imaging. The electrode configuration of MECT is standard bifrontal stimulation configuration, and the coil configuration of MST is circular. Maps of the ratio of the electric field strength to neural activation threshold are obtained to evaluate the stimulation strength and stimulation focality in brain regions. The stimulation strength induced by MECT is stronger than MST, and the activated region is wider. MECT stimulation strength in gray matter is 17.817 times of that by MST, and MECT stimulation strength in white matter is 23.312 times of that by MST. As well, MECT stimulation strength in hippocampi is 35.162 times of that by MST. More than 99.999% of the brain volume is stimulated at suprathreshold by MECT. However, MST activated only 0.700% of the brain volume. The stimulation strength induced by MECT is stronger than MST, and the activated region is wider may be the reason that MECT has better effectiveness. Nevertheless, the stronger stimulation strength in hippocampi induced by MECT may be the reason that MECT is more likely to give rise to side effects. Based on the results of this study, it is expected that a more accurate clinical quantitative treatment scheme should be studied in the future.

Artificial Liver and Renal Support System for Cynomolgus Monkeys with Surgery-Induced Acute Renal Failure: A Preclinical Study.

Renal dysfunction is one of the most common complications of liver cirrhosis and is associated with increased morbidity and mortality. However, no available technology can simultaneously support liver and renal function in these patients. The aim of this study was to evaluate the safety and efficacy of an artificial liver and renal support system in cynomolgus monkeys with surgery-induced ARF. The ARF model was established by ligature of bilateral renal arteries in eight cynomolgus monkeys, which were randomly divided into a treatment group (n = 4) and control group (n = 4). Biochemical indexes were determined before and after surgery. Blood endotoxin levels, biochemical indexes, and bacterial cultures were assessed at 0, 3, and 6 h during treatment. System pressures and vital signs were recorded at 1 h intervals. Pathological examination was performed after death. ARF was successfully established, based on significant elevation of biochemical indexes and pathological examination. The treatment group had significantly reduced biochemical indexes relative to the control group. Measurement of blood endotoxins and aerobic and anaerobic bacteria cultures indicated no bacterial growth. The system pressures and vital signs were stable during treatment. The results indicate that our support system for the treatment of cynomolgus monkeys with surgery-induced acute renal failure is safe and effective.

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.

[Progress in hepatocyte status detection and its application in bioartificial liver support system].

Bioartificial liver support system (BALSS) provides a new way to treat liver failure and leaves more time for patients who are waiting for liver transplantation. It has detoxification function as well as the human liver, at the same time it can provide nutrition and improve the internal environment inside human body. Bioreactors and hepatocytes with good biological activity are the cores of BALSS which determine the treatment effect. However, in the course of prolonged treatment, the function and activity of hepatocytes might be greatly changed which could influence the efficacy. Therefore, it is very important to detect the status of the hepatocytes in BALSS. This paper presents some common indicators of cell activity, detoxification and synthetic functions, and also introduces the commonly detection methods corresponding to each indicator. Finally, we summarize the application of detection methods of the hepatocyte status in BALSS and discuss its development trend.

High-frequency repetitive transcranial magnetic stimulation for treating moderate traumatic brain injury in rats: A pilot study.

Transcranial magnetic stimulation (TMS) is a method of noninvasive brain stimulation that causes neuromodulation by activating neurons or changing excitability in a certain brain area. Considering the known effects of TMS and the pathophysiology of traumatic brain injury (TBI), TMS was proposed to have potential for treating this condition. Moderate TBI was induced in adult male Sprague Dawley rats using Feeney's weight-dropping method. Injured rats were divided into a TMS group and a control group. Repetitive TMS (rTMS) was administered to rats in the TMS group from post-TBI day 2. At post-TBI days 7, 14 and 28, three or four of the rats were sacrificed, and harvested brains were embedded in paraffin and sectioned. Sections were then treated with hematoxylin and eosin and immunohistochemical staining. Three rats from each group underwent fludeoxyglucose F 18 micro-positron emission tomography scanning on post-TBI day 2 and 13. The unexpected mortality rate after injury was lower in the TMS group than in the control group. The modified neurological severity score of the TMS group was lower compared with the control group at post-TBI day 14. According to the results of hematoxylin eosin staining, relative cerebral parenchyma loss was lower at post-TBI day 28 in the TMS group compared with the control group. However, the aforementioned differences were not found to be statistically significant. There was also no significant difference in glucose metabolism between the two groups. According to immunohistochemical staining, the TMS group showed a significantly higher level of proliferation (indicated by bromodeoxyuridine) in the subventricular zone, as compared with the control group (P<0.05). A significantly higher rate of neuron survival at day 28 (P<0.05; indicated by NeuN) and a significantly reduced rate of apoptosis at days 7 and 14 (P<0.05; indicated by caspase-3) were observed in the perilesional zone of the TMS group, as compared with the control group. The current findings suggest that high-frequency rTMS may promote neurogenesis and provide a basis for further studies in this area.

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.

Simulation and experimental research on micro-channel for detecting cell status in bio-artificial liver.

BACKGROUND: Bioartificial liver support system (BALSS) based on culturing hepatocytes is an important research field for the treatment of acute liver failure. It is necessary to monitor the state of liver cell functions during the treatment of BALSS in order to guide clinical treatment. OBJECTIVE: To design a micro-channel chip to achieve flash mixing for timely detection of liver cell status in bioreactors and improving liver cells growth environment to ensure the efficacy of the bio-artificial liver support system. METHODS: Alanine aminotransferase (ALT) and Urea are chosen as detection indicators to reflect the degree of liver cell injury and the detoxification function. A diamond tandem structure micro-channel is designed and optimized to achieve the efficient mixing of serum and ALT or Urea reagent. RESULTS: The simulation and experimental results show that the diamond tandem structure micro-channel can significantly improve the mixing efficiency and meet the online detecting requirements. CONCLUSION: The easily controllable diamond tandem structure micro-channel combines the advantages of active and passive mixer and can effectively mix the serum and ALT or Urea reagent. It lays the foundation for online monitoring of liver cells and will help to improve the viability of liver cell in the bioreactor.

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.

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.

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.

Simulation of injury potential compensation by direct current stimulation in rat spinal cord.

Injury potential, a significant index of spinal cord injury (SCI), is generated by the movement of extracellular ions. It can be compensated through applied direct current (DC) stimulation, which prevents the influx of the free calcium, and eventually reduces the development of secondary injury. Therefore, the compensation of injury potential is beneficial to the repairing of the function of spinal cord. The compensation effect can be evaluated by whether the magnitudes of longitudinal electric fields (EFs) are compensated to zero. However, there have been no established criteria to determine the distribution and shape of stimulating electrodes. In this study, in order to optimize the stimulating electrodes, a finite element model (FEM) of rat spinal cord was developed, and the EFs changes induced by electrodes of different sizes, shapes and locations after SCI were calculated. All the designed configurations of electrodes were able to compensate injury potential, but the resultant compensation effects vary. Pin and disc electrodes produced uneven EFs, while ring electrodes produced uniformly distributed EFs. Moreover, large ring electrodes can compensate the longitudinal EFs almost to zero with relatively low current density (0.55 µA/mm(2)) applied. These results provide a basis for the determination of electrical stimulation parameters in the compensation of injury potential.

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.