WO2020216291A1 - 神经系统疾病治疗电场的发生装置 - Google Patents

神经系统疾病治疗电场的发生装置 Download PDF

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WO2020216291A1
WO2020216291A1 PCT/CN2020/086403 CN2020086403W WO2020216291A1 WO 2020216291 A1 WO2020216291 A1 WO 2020216291A1 CN 2020086403 W CN2020086403 W CN 2020086403W WO 2020216291 A1 WO2020216291 A1 WO 2020216291A1
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electric field
electrode
spatial
generating
space
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PCT/CN2020/086403
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English (en)
French (fr)
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乐飚
王丽江
唐万福
奚勇
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上海必修福企业管理有限公司
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0408—Use-related aspects
    • A61N1/0456—Specially adapted for transcutaneous electrical nerve stimulation [TENS]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/02—Details
    • A61N1/04—Electrodes
    • A61N1/0404—Electrodes for external use
    • A61N1/0472—Structure-related aspects
    • A61N1/0484—Garment electrodes worn by the patient
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/36025—External stimulators, e.g. with patch electrodes for treating a mental or cerebral condition

Definitions

  • the invention relates to a medical field, in particular to a device for generating an electric field for treating neurological diseases.
  • Nervous system diseases refer to diseases caused by pathological changes in the nervous system, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington disease (Huntington disease, HD), amyotrophic lateral cord Sclerosis (amyotrophic lateral sclerosis, ALS), epilepsy (epilepsy), etc.
  • PD Parkinson's disease
  • AD Alzheimer's disease
  • HD Huntington disease
  • ALS amyotrophic lateral cord Sclerosis
  • epilepsy epilepsy
  • Alzheimer's disease and Parkinson's disease are relatively common neurological diseases that affect human health. Their pathogenesis is more complicated, but they have certain commonalities. They can be summarized as neuronal apoptosis; the regulatory role of microglia ; The expression of miRNA; the regulation of autophagy and the degradation of P62 protein.
  • t DCS Transcranial direct current stimulation
  • TMS transcranial magnetic stimulation
  • tDCS modulates the transmembrane potential of nerve cells by releasing a weak current (1 ⁇ 2mA) in the scalp, leading to depolarization and hyperpolarization, thereby changing the excitability of the cerebral cortex.
  • tDCS has been used by clinicians and neuroscientists for treatment Mental and neurological diseases.
  • the stimulation sites include the left dorsolateral prefrontal cortex (DLPFC), the temporal lobe, and a combination of multiple areas.
  • DLPFC left dorsolateral prefrontal cortex
  • the stimulation sites include the left dorsolateral prefrontal cortex (DLPFC), the temporal lobe, and a combination of multiple areas.
  • DLPFC left dorsolateral prefrontal cortex
  • DCS can regulate neuronal activity and concussion activity, neurotransmitter transmission, cerebral blood flow, has synaptic and non-postsynaptic effects, and can change the pattern of brain function connections. But subjects occasionally reported side effects such as local tingling, itching, burning, pain and headache.
  • Deep brain stimulation is a type of electrical stimulation therapy for PD. Based on stereotactic technology, electrodes with better histocompatibility are placed in the patient's intracranial globus pallidus or subthalamic nucleus at specific locations , And connected with the nerve control device installed under the patient's skin as an internal device, the external remote controller can adjust the stimulation parameters to achieve the effect of nerve regulation. It is mainly used for patients with Parkinson's disease who suffer from movement fluctuations and drug-refractory tremor. It has the advantages of good selectivity, clear target, no injury, reversible, adjustable, safe operation and few complications, but related complications and unnatural Death is still inevitable.
  • the main surgical complications after DBS include seizures, temporary confusion, intracerebral hemorrhage, and pulmonary embolism; postoperative hardware-related complications are the most common non-hemodynamic complications, including infection, skin erosion, and lead Migration, lead breakage and failure, breakage and failure of other components, and failure of internal pulse generator.
  • the purpose of the present invention is to provide a device for generating an electric field for treating neurological diseases.
  • the present invention provides a device for generating an electric field for treating neurological diseases, the device at least comprising:
  • An electrode helmet the electrode helmet is a hollow cavity with one end open, the inner wall of the electrode helmet is provided with a spatial electric field outer electrode, and the spatial electric field outer electrode is used to form a spatial electric field between the spatial electric field contact electrode, and
  • the outer electrode of the space electric field includes more than two different electrodes; the position of each different electrode is adjustable to adjust the coverage area of the space electric field.
  • the second aspect of the present invention provides a method for generating a spatial electric field, which at least includes the following steps:
  • the third aspect of the present invention provides a method of using the aforementioned device for generating an electric field for treating neurological diseases, the method at least including the following steps:
  • the fourth aspect of the present invention provides the use of the aforementioned apparatus for generating an electric field for the treatment of neurological diseases or the aforementioned method for generating an electric field in space in intervention in the process of neuron transmission electrons.
  • the device for generating an electric field for treating neurological diseases of the present invention has the following beneficial effects:
  • the device for generating an electric field for treating neurological diseases of the present invention uses the equipotential of one pole of the electric field to connect to the human body, and the opposite pole establishes a corresponding electric field in space, so as to get rid of contact electrodes or implant electrodes.
  • different electrodes form multiple matrix electrodes to form multiple electric fields with different positions, strengths, frequencies, and waveforms, forming a three-dimensional structure electric field effect Nerve cells or tissues. Differentiately control nerve cells or tissues in different locations or provide different ways of control.
  • the opposite poles are distributed on clothing, shoes and hats, etc., which have a long-term uninterrupted effect on nerve formation. The applicability is stronger and the treatment effect is better. The safety performance is higher.
  • Fig. 1 is a schematic diagram of the structure of the generating device of the electric field for treating neurological diseases of the present invention.
  • Fig. 2 is a schematic diagram showing the arrangement of different electrodes of the external electrodes of the spatial electric field of the present invention.
  • Figure 3 Observation of the neuron pathological results and phosphorylated tau protein expression in the CA1 area of the rat hippocampus under a light microscope.
  • Figure 4 shows the results of expression levels of TH and ⁇ -syn in Westernblo substantia nigra.
  • the experimental methods, detection methods, and preparation methods disclosed in the present invention all adopt conventional molecular biology, biochemistry, chromatin structure and analysis, analytical chemistry, cell culture, recombinant DNA technology and related fields in the technical field. Conventional technology.
  • the present invention provides a device for generating an electric field for treating neurological diseases, the device at least comprising:
  • An electrode helmet the electrode helmet is a hollow cavity with one end open, the inner wall of the electrode helmet is provided with a spatial electric field outer electrode, and the spatial electric field outer electrode is used to form a spatial electric field between the spatial electric field contact electrode, and
  • the outer electrode of the space electric field includes more than two different electrodes; the position of each different electrode is adjustable to adjust the coverage area of the space electric field.
  • the spatial electric field contact electrode is used to connect with the object to be measured, so that the object to be measured and the spatial electric field contact electrode are equipotential.
  • the object to be tested is a living animal. Further, it is a mammal.
  • the mammals are preferably rodents, artiodactyls, odd-hoofed animals, lagomorphs, primates and the like.
  • the primates are preferably monkeys, apes or humans.
  • the spatial electric field contact electrode is grounded.
  • the electrode helmet is not in contact with the object to be detected.
  • the outer electrode of the spatial electric field does not contact the object to be detected either.
  • the head of the object to be detected can be deep into the cavity of the electrode helmet.
  • the generating device further includes:
  • the power supply is used to provide electrical energy to the generating device
  • the control unit is used to adjust and control the performance of the space electric field, including one or more of electric field strength, electric field direction, electric field pulse frequency, and electric field range.
  • control unit can adjust the frequency, waveform, and amplitude of the power supply, so as to output the target high voltage, frequency, and waveform. Changes the intensity, frequency and vibration of the energy acting on the cells. Distinguish the difference between normal tissues and controlled tissues.
  • control unit can adjust the frequency, size, and waveform of the voltage to generate the target electric field intensity. By adjusting the intensity of the target electric field, the effects on different types of tissues and cells can be achieved.
  • the control unit can be used to select different electrodes for power supply, so as to adjust the effect area and electric field intensity of the spatial electric field. By detecting the change of the electric field coupling current, it is possible to track the range, depth and position of the electric field.
  • the spatial electric field contacting the electrode does not affect the selection of the position of the different electrode or the electrification situation.
  • the position and/or spatial electric field performance of the different electrode is confirmed according to other diagnostic data; and/or, the position, number, and/or spatial electric field performance of the different electrode is diagnosed according to the electric field coupling current. Automatic tracking adjustment.
  • water is used as a conductive contact between the spatial electric field contact electrode and the object to be detected.
  • the power supply is a high-voltage output power supply.
  • the voltage of the power supply is adjustable from 0.001 kV to 120 kV
  • the current output is adjustable from 0.001 mA to 10000 mA
  • the working distance of the electric field is adjustable from 0.1 cm to 100 cm.
  • the different electrode is a point probe.
  • the different electrodes may be arranged to form a matrix of different electrodes to form a spatial lattice electric field, and the spatial lattice output electric field is precisely controlled according to the drug action range or related medical imaging data to adapt to the action range.
  • the arrangement of the different electrodes can be selected from a lattice arrangement, which can be a 2n lattice, where n is a non-zero natural number.
  • n is a non-zero natural number.
  • the density of lattice depends on the accuracy of electric field action. The use of precise electric field to improve the efficiency of nerve cells and reduce the effect on normal tissues. However, limited by the size of the output electric field power supply, the lattice is dense and the power supply is bulky.
  • any one or more warp lines from a ⁇ b ⁇ c to xx and any one or more weft lines from 1 ⁇ 2 ⁇ 3 to nn activate one or more lattice different poles, and these different electrodes and equal potential electrodes constitute a function Electric field, electric field coverage is determined by the activated lattice pole.
  • This range can come from the coupling characteristics of nerve cells in the electric field or other digital signals of medical diagnostic imaging. It is confirmed that this electric field range can accurately act on nerve cells and reduce the impact on other tissues.
  • a 64 dot matrix can only distinguish 64 electric field positions
  • a 4096 dot matrix can distinguish 4096 electric field positions
  • a 16777216 dot matrix can distinguish 16777216 electric field positions. The effect of this dot matrix is relatively accurate, and the image of the surrounding normal tissues is small.
  • the helmet is made of insulating material.
  • the cavity of the electrode helmet is a hemispherical cavity. It is suitable for placing on the head of the living body to be tested.
  • an electrode groove is provided on the inner wall of the electrode helmet; it is used to install a different electrode.
  • the electrode slot is detachably connected to the different electrode.
  • the size of the electrode helmet is adjustable. Suitable for different living bodies to be tested.
  • the present invention also provides a method for generating a spatial electric field, which at least includes the following steps:
  • the living organism refers to a living animal. Further, it is a mammal.
  • the mammals are preferably rodents, artiodactyls, odd-hoofed animals, lagomorphs, primates and the like.
  • the primates are preferably monkeys, apes or humans.
  • the method further includes adjusting and controlling the performance of the spatial electric field, including one or more of electric field strength, electric field direction, electric field pulse frequency, and electric field lattice range.
  • the spatial electric field contact electrode is grounded.
  • the different electrode is a point probe.
  • the arrangement of the different electrodes is selected from a lattice arrangement, which is a 2 n lattice, where n is a non-zero natural number.
  • n is a non-zero natural number.
  • 64 dot matrix 4096 dot matrix
  • 16777216 dot matrix etc.
  • the density of lattice depends on the accuracy of electric field action.
  • water is used as a conductive contact between the spatial electric field contact electrode and the living organism.
  • the electrode helmet is not in contact with the living organism.
  • the external electrode of the spatial electric field does not interact with the living organism.
  • the head can be deep into the cavity of the electrode helmet. As long as the electrode helmet is in contact with the living organism.
  • the voltage of the power supply is adjustable from 0.001 kV to 120 kV
  • the current output is adjustable from 0.001 mA to 10000 mA
  • the working distance of the electric field is adjustable from 0.1 cm to 100 cm.
  • the present invention also provides a method of using the aforementioned device for generating an electric field for treating neurological diseases, and the method at least includes the following steps:
  • the object to be tested is a living animal. Further, it is a mammal.
  • the mammals are preferably rodents, artiodactyls, odd-hoofed animals, lagomorphs, primates and the like.
  • the primates are preferably monkeys, apes or humans.
  • placing the electrode helmet above the object to be detected refers to placing the electrode helmet above the head of the object to be detected.
  • the spatial electric field contact electrode is grounded.
  • the electrode helmet is not in contact with the object to be detected.
  • the outer electrode of the spatial electric field does not contact the object to be detected either.
  • the head of the object to be detected can be deep into the cavity of the electrode helmet.
  • the generating device further includes:
  • the power supply is used to provide electrical energy to the generating device
  • the regulating unit is used to regulate and control the performance of the space electric field, including one or more of electric field strength, electric field direction, electric field pulse frequency, and electric field lattice range.
  • control unit can adjust the frequency, waveform, and amplitude of the power supply, so as to output the target high voltage, frequency, and waveform. Changes the intensity, frequency and vibration of the energy acting on the cells. Distinguish the difference between normal tissues and controlled tissues.
  • control unit can adjust the frequency, size, and waveform of the voltage to generate the target electric field intensity. By adjusting the intensity of the target electric field, the effects on different types of tissues and cells can be achieved.
  • the control unit can be used to select different electrodes for power supply, so as to adjust the effect area and electric field intensity of the spatial electric field. By detecting the change of the electric field coupling current, it is possible to track the range, depth and position of the electric field.
  • the spatial electric field contacting the electrode does not affect the selection of the position of the different electrode or the electrification situation.
  • the position and/or spatial electric field performance of the different electrode is confirmed according to other diagnostic data; and/or, the position, number, and/or spatial electric field performance of the different electrode is diagnosed according to the electric field coupling current. Automatic tracking adjustment.
  • water is used as a conductive contact between the spatial electric field contact electrode and the object to be detected.
  • the power supply is a high-voltage output power supply.
  • the voltage of the power supply is adjustable from 0.001 kV to 120 kV
  • the current output is adjustable from 0.001 mA to 10000 mA
  • the working distance of the electric field is adjustable from 0.1 cm to 100 cm.
  • the different electrode is a point probe.
  • the different electrodes may be arranged to form a matrix of different electrodes to form a spatial lattice electric field, and the spatial lattice output electric field is precisely controlled according to the drug action range or related medical imaging data to adapt to the action range.
  • the arrangement of the different electrodes can be selected from a lattice arrangement, which can be a 2n lattice, where n is a non-zero natural number.
  • n is a non-zero natural number.
  • the density of lattice depends on the accuracy of electric field action. The use of precise electric field to improve the efficiency of nerve cells and reduce the effect on normal tissues. However, limited by the size of the output electric field power supply, the lattice is dense and the power supply is bulky.
  • any one or more warp lines from a ⁇ b ⁇ c to xx and any one or more weft lines from 1 ⁇ 2 ⁇ 3 to nn activate one or more lattice different poles, and these different electrodes and equal potential electrodes constitute a function Electric field, electric field coverage is determined by the activated lattice pole.
  • This range can come from the coupling characteristics of nerve cells in the electric field or other digital signals of medical diagnostic imaging. It is confirmed that this electric field range can accurately act on nerve cells and reduce the impact on other tissues.
  • a 64 dot matrix can only distinguish 64 electric field positions
  • a 4096 dot matrix can distinguish 4096 electric field positions
  • a 16777216 dot matrix can distinguish 16777216 electric field positions. The effect of this dot matrix is relatively accurate, and the image of the surrounding normal tissues is small.
  • the present invention also provides the use of the aforementioned device for generating an electric field for the treatment of neurological diseases or the aforementioned method for generating a space electric field in intervention in the process of neuron transmission electrons.
  • Experiment 1 Find the optimal range of change of the inter-electrode intensity for the treatment of Alzheimer's disease.
  • SD rats Healthy Sprague-Dawley (SD) rats were trained in Morris water maze in groups, and the escape latency and average swimming speed were detected. Those with larger differences in learning and memory ability and swimming were eliminated.
  • Rats were intraperitoneally injected with 1.25% D-galactose (50mg/kg/d) for 6 weeks to cause aging.
  • the control group was intraperitoneally injected with equal volume of normal saline.
  • (2) Dilute A ⁇ 25-35 to 10 ⁇ g/ ⁇ l in physiological saline, and incubate at 37°C for 1w to make it into aggregated A ⁇ 25-35.
  • a ⁇ 25-35 injection was started on the second day after D-galactose was continuously treated for 2-3w.
  • SD rats were anesthetized with 10% chloral hydrate (300mg/kg intraperitoneal injection) and fixed on the stereotaxic instrument, and the head was cut Skin, expose the skull.
  • Inclusion criteria Morris water maze test was performed, and the method was the same as before.
  • the performance of rats in each group was basically stable during the adaptation training to the escape latency period.
  • the average escape latency of the mouse is the reference value, and the difference between the average escape latency of each rat and the reference value is calculated as the ratio of the average escape latency of the mouse. If the value is more than 20%, the mouse is considered to be a successful model.
  • 10 healthy rats in group H as the control group.
  • the surface electrode is designed as a circular stimulation electrode with a diameter of 0.2cm and an anode
  • the working distance between the rats and the treated rats is adjustable from 0.1cm to 100cm.
  • the two levels are placed on both sides of the hippocampus for continuous stimulation for 24 hours with an interval of 2 to 3 seconds.
  • Table 1 Summary of the grouping situation after the experimental rat water maze verification
  • the rats in each experimental group and control group described in Table 1 were treated with corresponding spatial electric field.
  • the duration is 24hr.
  • the rats pass the Morris water maze experiment to verify the effect of space electric field treatment.
  • Table 2 Summary of escape time verified by water maze after space electric field treatment
  • HE staining was used to observe the cell morphology and phosphorylated tau protein immunohistochemistry in CA1 area, and the average optical density of positive cells was measured in a 400-fold visual field.
  • the Morris water maze test was performed on each group of rats before the operation to determine the cognitive function. After the water maze test, the rats were sacrificed, the hippocampus of the rats were taken, and the rats' hippocampus were observed under a light microscope.
  • the PD rat model was prepared by subcutaneous injection of rotenone on the back of the neck.
  • the model group and the electroacupuncture treatment group were given rotenone (2mg/kg, dissolved in sunflower oil, concentration 2mg/mL) subcutaneous injection on the back of the neck , Once a day for 28 days; the normal group does not do any treatment; the sham operation group is the same as the model group, but only the same amount of sunflower oil emulsion (solvent) without rotenone is injected; the electric field pretreatment group first treats normal rats The electric field was treated for 7 days, and then the model was built.
  • the scoring criteria are as follows, 1 is divided into rats with weakened resisting behavior, arched back, vertical hair, yellow and dirty hair, and reduced active activities; 2 is divided into 1 point, and the reduction in active activities is more obvious, accompanied by tremor , Slow movement, or unstable gait; 4 points for performance with 2 points, and unstable gait, or unable to walk in a straight line, or rotate to one side when walking; 6 points for unilateral reclining, unilateral Paralysis of the forelimbs or hind limbs, difficulty in walking, and difficulty in eating; 8 points for complete paralysis of unilateral limbs (forelimbs or hind limbs), spasms of limbs, weight loss, inability to eat; 10 points for dying state or death. In this study, 6 rats were randomly selected from the rats with behavioral scores of 2-8 points and used TH immunohistochemistry for histological identification.
  • the rats that died and had unqualified behavioral scores were excluded, and 12 rats in each group were included in the specimen collection. After weighing, the rats were anesthetized with 10% chloral hydrate by intraperitoneal injection, the dose was 0.2mL/100g.
  • Six rats in each group were randomly selected for internal fixation with paraformaldehyde in the left ventricle. The substantia nigra tissue of the midbrain was taken and fixed overnight with 4% paraformaldehyde for paraffin-embedded sections for morphological observation. The other 6 rats were quickly decapitated after they were completely anesthetized.
  • the brain tissue was quickly removed from the ice surface and the substantia nigra block was separated.
  • the substantia nigra block was wrapped in tin foil and placed in liquid nitrogen for quick freezing.
  • the tissue was taken out and placed in a cryotube at -80°C in the refrigerator for testing.
  • Immunohistochemistry was used to detect the positive expression of substantia nigra TH and ⁇ -syn.
  • the above sections were subjected to conventional dewaxing treatment, and the sections were put into xylene I-xylene II-anhydrous ethanol I-anhydrous ethanol II-95% ethanol-90% ethanol-80% ethanol-70% ethanol, and then put into distilled water Soak for 2min.
  • Microwave is used for antigen retrieval; 3% H2O2 freshly prepared with distilled water is added dropwise to the sliced tissue to block endogenous peroxidase, rinsed with PBS 3 times, 3 minutes each time; under microscope observation, use a spatula to remove the ROI After the neighborhood was minced, PBS was added to extract samples under centrifugal conditions, and Westernblot was used to detect the expression levels of TH and ⁇ -syn ( Figure 4).

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Abstract

一种神经系统疾病治疗电场的发生装置，所述发生装置至少包括：空间电场接触电极；电极头盔，所述电极头盔为一端开口的中空腔体，所述电极头盔内壁设有空间电场外电极，所述空间电场外电极用于与所述空间电场接触电极之间形成空间电场，所述空间电场外电极包括2个以上异电极；各个异电极的位置可调，用于调整空间电场的覆盖面积。该神经系统疾病治疗电场的发生装置，适用性更强，治疗效果更好，安全性能更高。

Description

神经系统疾病治疗电场的发生装置 技术领域
本发明涉及一种医疗领域，特别是涉及一种神经系统疾病治疗电场的发生装置。
背景技术
神经系统疾病是指神经系统发生病变引发的疾病，主要包括帕金森病(Parkinson’s disease,PD)、阿尔茨海默病(Alzheimer’s disease,AD)、亨廷顿病(Huntington disease，HD)、肌萎缩侧索硬化症(amyotrophic lateral sclerosis，ALS)、癫痫(epilepsy)等。
阿尔兹海默病与帕金森病均是比较常见的影响人类健康的神经系统疾病，其发病机制较为复杂，但具有一定的共性，归纳总结为神经元的凋亡；小胶质细胞的调节作用；miRNA的表达；自噬过程的调节作用及P62蛋白的降解作用。
随着人口老龄化的加速，AD严重威胁着老年人的健康和生活质量。在我国，60岁以上人群中AD患病率约为1.6％，全世界有0.468亿AD患者，预计2030将增加到0.747亿人。经颅直流电刺激(transcranial direct current stimulation，t DCS)是非侵入性神经调控技术之一，相比于经颅磁刺激(transcranial magnetic stimulation，TMS)其安全性更好，便携经济，容易操作，具有居家治疗的潜力。tDCS通过在头皮释放微弱的电流(1～2mA)调节神经细胞跨膜电位，导致去极化和超极化，从而改变大脑皮质的兴奋性，因此t DCS已被临床医师和神经科学家用于治疗精神和神经疾病。近十年来发现tDCS可有助于AD的治疗，刺激部位包括左侧背外侧前额叶皮质(left dorsolateral prefrontal cortex，DLPFC)、颞叶以及多个区域的组合。t DCS能调节神经元活性及脑震荡活性、神经递质传递、脑血流量，具有突触和非突触后作用并能改变脑功能连接模式。但是被试者偶尔会报告副作用，如局部刺痛、瘙痒、灼痛、疼痛和头痛。
脑深部电极植入(deep brain stimulation，DBS)术是治疗PD的一种电刺激疗法，基于立体定向技术，将组织相容性较好的电极置于患者颅内苍白球或丘脑底核特定位置，并与安装于患者皮下的神经调控装置相连作为体内装置，体外遥控器可通过调节刺激参数以达到神经调节的效果。主要用于运动波动和药物难治性震颤的帕金森病患者，具有选择性好、靶点明确、无损伤、可逆、可调节、手术安全和并发症少等优点，但相关并发症和非自然死亡仍不可避免。DBS术后外科手术并发症主要有癫痫发作、暂时性意识模糊、脑内出血和肺栓塞等；术后硬件相关并发症是最常见的非血流动力学并发症，主要有感染和皮肤侵蚀、铅迁移、引线 断裂和失效、其他部件断裂和失效以及内部脉冲发生器失效等。
发明内容
鉴于以上所述现有技术的缺点，本发明的目的在于提供一种神经系统疾病治疗电场的发生装置。
为实现上述目的及其他相关目的，本发明提供一种神经系统疾病治疗电场的发生装置，所述发生装置至少包括：
空间电场接触电极；
电极头盔，所述电极头盔为一端开口的中空腔体，所述电极头盔内壁设有空间电场外电极，所述空间电场外电极用于与所述空间电场接触电极之间形成空间电场，所述空间电场外电极包括2个以上异电极；各个异电极的位置可调，用于调整空间电场的覆盖面积。
本发明第二方面提供一种空间电场的发生方法，至少包括以下步骤：
1)使空间电场接触电极接触生物活体；
2)将电极头盔置于所述生物活体的头部上方；
3)调节空间电场外电极的2个以上异电极的位置，用于调整空间电场的覆盖面积；
4)将所述空间电场接触电极及所述空间电场外电极接通电源，产生空间电场。
本发明第三方面提供前述神经系统疾病治疗电场的发生装置的使用方法，所述方法至少包括如下步骤：
1)将待检测对象空间电场接触电极连接，使待测对象与所述空间电场接触电极形成等电位；
2)将电极头盔置于所述待检测对象的上方；
3)调整各个异电极的位置，以调整空间电场的覆盖面积。
本发明第四方面提供前述神经系统疾病治疗电场的发生装置或前述空间电场的发生方法在在神经元传输电子过程干预中的用途。
如上所述，本发明神经系统疾病治疗电场的发生装置，具有以下有益效果：
本发明所述神经系统疾病治疗电场的发生装置，利用电场一极等电位接入人体，异极在空间建立对应电场，从而摆脱接触电极或植入电极。通过改变电压、频率以及波形，阻断、扰动、神经元传输电子，从而影响神经传递；异电极组成多个矩阵电极，形成多个不同位置、强度、频率、波形的电场，形成立体结构电场作用神经细胞或组织。区别控制不同位置的神经细胞或组织或提供不同方式的控制作用。(4)头盔式电极的设计方法，异极分布在服装、鞋帽等物件上，对神经形成长期不间断的作用。适用性更强，治疗效果更好。安全性能更高。
附图说明
图1显示为本发明神经系统疾病治疗电场的发生装置结构示意图。
图2显示为本发明空间电场外电极的异电极的排布方式示意图。
图3光镜下观察大鼠海马组织CA1区神经元病理学结果和磷酸化tau蛋白表达情况。
图4用Westernblo黑质TH及α-syn表达程度结果图。
具体实施方式
以下由特定的具体实施例说明本发明的实施方式，熟悉此技术的人士可由本说明书所揭露的内容轻易地了解本发明的其他优点及功效。
请参阅图1至图4。须知，本说明书所附图式所绘示的结构、比例、大小等，均仅用以配合说明书所揭示的内容，以供熟悉此技术的人士了解与阅读，并非用以限定本发明可实施的限定条件，故不具技术上的实质意义，任何结构的修饰、比例关系的改变或大小的调整，在不影响本发明所能产生的功效及所能达成的目的下，均应仍落在本发明所揭示的技术内容能涵盖的范围内。同时，本说明书中所引用的如“上”、“下”、“左”、“右”、“中间”及“一”等的用语，亦仅为便于叙述的明了，而非用以限定本发明可实施的范围，其相对关系的改变或调整，在无实质变更技术内容下，当亦视为本发明可实施的范畴。
除非另外说明，本发明中所公开的实验方法、检测方法、制备方法均采用本技术领域常规的分子生物学、生物化学、染色质结构和分析、分析化学、细胞培养、重组DNA技术及相关领域的常规技术。
如图1所示，本发明提供一种神经系统疾病治疗电场的发生装置，所述发生装置至少包括：
空间电场接触电极；
电极头盔，所述电极头盔为一端开口的中空腔体，所述电极头盔内壁设有空间电场外电极，所述空间电场外电极用于与所述空间电场接触电极之间形成空间电场，所述空间电场外电极包括2个以上异电极；各个异电极的位置可调，用于调整空间电场的覆盖面积。
进一步的，所述空间电场接触电极用于与待测对象相连接，使待测对象与所述空间电场接触电极形成等电位。
所述待测对象为动物活体。进一步的，为哺乳动物。所述哺乳动物优选为啮齿目动物、偶蹄目动物、奇蹄目动物、兔形目动物、灵长目动物等。所述灵长目动物优选为猴、猿或人。
在一种实施方式中，所述空间电场接触电极接地。
进一步的，所述电极头盔不与所述待检测对象接触。同时，所述空间电场外电极也不与 所述待检测对象接触。在一种实施方式中，可以使待检测对象的头部深入到所述电极头盔腔体内。
在一种实施方式中，所述发生装置还包括：
供电电源，用于给所述发生装置提供电能；
调控单元，用于调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种。
在一种实施方式中，所述调控单元可以对电源的频率、波形、幅度调整，从而输出目标高压、频率、波形。使作用在细胞上的能量强度、频次、震动发生变化。区别正常组织以及被控组织的作用差异。
在一种实施方式中，所述调控单元可以对电压的频率、大小以及波形进行调整，从而产生目标电场强度。通过对目标电场强度的调整，实现分别对不同类型组织以及细胞的作用。
可以利用所述调控单元选择给不同的异电极进行供电，以便调节空间电场的作用区域及电场强度。通过检测电场耦合电流变化，可以跟踪电场作用范围、电场的作用深度与位置。
空间电场接触电极不影响异电极位置或通电情况的选择。
在一种实施方式中，所述异电极的位置和/或空间电场的性能根据其他诊断数据确认；和/或，所述异电极的位置、数量和/或空间电场性能根据电场耦合电流诊断后自动跟踪调整。
在一种实施方式中，所述空间电场接触电极与待检测对象之间通过水作为导电接触。
在一种实施方式中，所述供电电源为高压输出电源。
在一种实施方式中，所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm。
在一种实施方式中，所述异电极为点状探头。
在一种实施方式中，所述异电极可以排布形成矩阵异电极，来组成空间点阵电场，根据药物作用范围或相关医学影像学数据，精确控制空间点阵输出电场，适应作用范围。
在一种实施方式中，所述异电极的排布方式可选自点阵排布，可以为2 n的点阵，其中n为非0自然数。例如64点阵、4096点阵、16777216点阵等，如图2所示。点阵密集程度取决于电场作用精确度。利用精确作用电场提高对神经细胞作用效率、减少对正常组织作用影响。但受输出电场电源体积限制，点阵密集而电源体积庞大。其中a\b\c一直到xx的任意一或多条经线和1\2\3一直到nn任意一或多条纬线激活一个或多个点阵异极，这些异电极和等电位电极组成作用电场，电场覆盖范围是激活的点阵极决定的。这个范围可以来自神经细胞在电场中的耦合特性或其他医学诊断影像数字信号。确认了这个电场范围，可以精确作用神 经细胞，减少对其他组织影响。一般64点阵只能区分64个电场位置，4096点阵可以区分4096个电场位置，16777216点阵可以分辨16777216个电场位置，这个点阵作用就相对精确，对周围正常组织影像就较小。
在一种实施方式中，所述头盔为绝缘材料。
在一种实施方式中，所述电极头盔的空腔为半球形空腔。适于放置于待检测活体的头部上方。
在一种实施方式中，所述电极头盔内壁设有电极槽；用于安装异电极。
所述电极槽与所述异电极可拆卸连接。
在一种实施方式中，所述电极头盔的大小可调节。适用于不同的待检测活体。
本发明还提供空间电场的发生方法，至少包括以下步骤：
1)使空间电场接触电极接触生物活体；
2)将电极头盔置于所述生物活体的头部上方；
3)调节空间电场外电极的2个以上异电极的位置，用于调整空间电场的覆盖面积；
4)将所述空间电场接触电极及所述空间电场外电极接通电源，产生空间电场。
所述生物活体是指动物活体。进一步的，为哺乳动物。所述哺乳动物优选为啮齿目动物、偶蹄目动物、奇蹄目动物、兔形目动物、灵长目动物等。所述灵长目动物优选为猴、猿或人。
进一步的，所述方法还包括调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场点阵范围中的一种或多种。
在一种实施方式中，所述空间电场接触电极接地。
在一种实施方式中，所述异电极为点状探头。
在一种实施方式中，所述异电极的排布方式选自点阵排布，为2 n点阵，其中n为非0自然数。例如64点阵、4096点阵、16777216点阵等，如图2所示。点阵密集程度取决于电场作用精确度。
在一种实施方式中，所述空间电场接触电极与生物活体之间通过水作为导电接触。
在一种实施方式中，所述电极头盔不与所述生物活体接触。同时，所述空间电场外电极也不与所述生物活体。在一种实施方式中，可以使头部深入到所述电极头盔腔体内。只要所述电极头盔与所述生物活体接触即可。
在一种实施方式中，所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm。
本发明还提供前述神经系统疾病治疗电场的发生装置的使用方法，所述方法至少包括如 下步骤：
1)将待检测对象空间电场接触电极连接，使待测对象与所述空间电场接触电极形成等电位；
2)将电极头盔置于所述待检测对象的上方；
3)调整各个异电极的位置，以调整空间电场的覆盖面积。
进一步的，所述待测对象为动物活体。进一步的，为哺乳动物。所述哺乳动物优选为啮齿目动物、偶蹄目动物、奇蹄目动物、兔形目动物、灵长目动物等。所述灵长目动物优选为猴、猿或人。
进一步的，将电极头盔置于所述待检测对象的上方是指，将电极头盔置于所述待检测对象的头部上方。
在一种实施方式中，所述空间电场接触电极接地。
进一步的，所述电极头盔不与所述待检测对象接触。同时，所述空间电场外电极也不与所述待检测对象接触。在一种实施方式中，可以使待检测对象的头部深入到所述电极头盔腔体内。
在一种实施方式中，所述发生装置还包括：
供电电源，用于给所述发生装置提供电能；
调控单元，用于调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场点阵范围中的一种或多种。
在一种实施方式中，所述调控单元可以对电源的频率、波形、幅度调整，从而输出目标高压、频率、波形。使作用在细胞上的能量强度、频次、震动发生变化。区别正常组织以及被控组织的作用差异。
在一种实施方式中，所述调控单元可以对电压的频率、大小以及波形进行调整，从而产生目标电场强度。通过对目标电场强度的调整，实现分别对不同类型组织以及细胞的作用。
可以利用所述调控单元选择给不同的异电极进行供电，以便调节空间电场的作用区域及电场强度。通过检测电场耦合电流变化，可以跟踪电场作用范围、电场的作用深度与位置。
空间电场接触电极不影响异电极位置或通电情况的选择。
在一种实施方式中，所述异电极的位置和/或空间电场的性能根据其他诊断数据确认；和/或，所述异电极的位置、数量和/或空间电场性能根据电场耦合电流诊断后自动跟踪调整。
在一种实施方式中，所述空间电场接触电极与待检测对象之间通过水作为导电接触。
在一种实施方式中，所述供电电源为高压输出电源。
在一种实施方式中，所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm。
在一种实施方式中，所述异电极为点状探头。
在一种实施方式中，所述异电极可以排布形成矩阵异电极，来组成空间点阵电场，根据药物作用范围或相关医学影像学数据，精确控制空间点阵输出电场，适应作用范围。
在一种实施方式中，所述异电极的排布方式可选自点阵排布，可以为2 n的点阵，其中n为非0自然数。例如64点阵、4096点阵、16777216点阵等，如图2所示。点阵密集程度取决于电场作用精确度。利用精确作用电场提高对神经细胞作用效率、减少对正常组织作用影响。但受输出电场电源体积限制，点阵密集而电源体积庞大。其中a\b\c一直到xx的任意一或多条经线和1\2\3一直到nn任意一或多条纬线激活一个或多个点阵异极，这些异电极和等电位电极组成作用电场，电场覆盖范围是激活的点阵极决定的。这个范围可以来自神经细胞在电场中的耦合特性或其他医学诊断影像数字信号。确认了这个电场范围，可以精确作用神经细胞，减少对其他组织影响。一般64点阵只能区分64个电场位置，4096点阵可以区分4096个电场位置，16777216点阵可以分辨16777216个电场位置，这个点阵作用就相对精确，对周围正常组织影像就较小。
本发明还提供前述神经系统疾病治疗电场的发生装置或前述空间电场的发生方法在在神经元传输电子过程干预中的用途。
实验方案
实验一：寻找治疗阿尔兹海默病最优的电极间强度的变化范围。
1、实验动物筛选
健康Sprague-Dawley(SD)大鼠，分组前行Morris水迷宫训练并检测逃避潜伏期及平均游泳速度，将学习记忆能力及游泳差异较大者剔除。
2、建立AD动物模型
(1)大鼠腹腔注射1.25％D-半乳糖(50mg/kg/d)，连续6w致衰老，对照组腹腔注射等容积生理盐水。(2)生理盐水将Aβ25-35稀释为10μg/μl，37℃孵育1w，使其变为聚集状态的Aβ25-35。在D-半乳糖连续处理2-3w后的第2天起行Aβ25-35注射，SD大鼠用10％水合氯醛(300mg/kg腹腔注射麻醉后固定于立体定位仪上，切开头部皮肤，暴露颅骨。根据Paxinos的《大鼠脑立体定位图》，选择右侧侧脑室为注射靶区，于前囟向后1.0mm，中线旁开1.7mm，深度3.8mm处用微型电钻开颅骨，暴露硬脑膜，微量进样器缓慢将10μg Aβ25-35注入，注射时间为10min，留针10min，使Aβ25-35充分弥散；缝合皮肤，大鼠放回鼠笼中常规饲养。 对照组注入等容积生理盐水。(3)1w后行水迷宫测试，选取痴呆大鼠纳入实验。纳入标准:行Morris水迷宫实验，方法同前，各组大鼠适应训练至逃避潜伏期成绩基本稳定，以正常组大鼠逃避潜伏期的平均值为参考值，计算每只大鼠的平均逃避潜伏期与参考值之差所占该鼠的平均逃避潜伏期比值。该值＞20％则认定该鼠为造模成功大鼠。
3、分组及实验步骤
共获得符合标准的痴呆大鼠70只，随机分为电场治疗组(根据参数电压不同分为A-G组共6组，分别实施0KV、0.1KV、1KV、3KV、10KV、30KV、120KV不同电场强度下的治疗验证(n＝10)。另行准备H组10只健康大鼠为对照组。采用本发明的神经系统疾病治疗电场的发生装置，将表面电极设计成圆形刺激电极，直径0.2cm，阳极与治疗大鼠间工作距离为可调的0.1cm-100cm。经颅电刺激治疗时，两级分别置于双侧海马区两侧，连续刺激24hr，刺激间隔2～3秒。
表1：实验用大鼠水迷宫验证后分组情况汇总
Figure PCTCN2020086403-appb-000001
水迷宫验证结果显示，腹腔注射等容积生理盐水的对照组大鼠，通过水迷宫的平均时间约68.2秒(n＝10)；D-半乳糖连续处理2周后进入痴呆症状的实验组大鼠，穿过同样的水迷宫的平均时间约210.5秒(n＝70)，约为对照组的3倍。
4、Morris水迷宫实验
对表1所述各实验组，对照组的大鼠，实施相应的空间电场治疗。持续时间为24hr，治疗后大鼠通过Morris水迷宫实验，对比验证空间电场治疗的效果。
表2：空间电场治疗后水迷宫验证的逃逸时间汇总
Figure PCTCN2020086403-appb-000002
治疗前水迷宫验证显示，对照组大鼠通过水迷宫的平均时间约70.1秒(n＝10)；治疗用电压低于1KV时，几乎没有治疗效果。当电场强度达到3KV时，开始出现轻微疗效。继续调整电场强度到10KV，30KV时，疗效持续提高，当电场强度达到120KV时，治疗效果与对照组几乎一致。这一验证结果暗示，空间电场治疗模式，有望给老年痴呆，脑组织损伤，植物人的康复治疗带来革命性的预后效果。
5、大鼠海马CA1区组织HE染色及磷酸化tau蛋白表达
1％水合氯醛腹腔麻醉；4％多聚甲醛250ml灌注固定，取出脑组织，4％多聚甲醛溶液常温下避光保存，石蜡包埋，取海马CA1区组织快速连续切片5片，分别作HE染色观察CA1区细胞形态及磷酸化tau蛋白免疫组化，在400倍视野下测定阳性细胞平均光密度值。如图3所示，于术前对各组大鼠进行Morris水迷宫实验测定认知功能,水迷宫测试结束后处死大鼠,取大鼠海马组织,进行HE染色,光镜下观察大鼠海马组织CA1区神经元病理学结果和磷酸化tau蛋白表达情况。未注射鱼藤酮的对照组大鼠模型HE染色后，大鼠海马CA1区神经元形态和结构未见异常，tau蛋白表达情况正常。
实验二：寻找治疗帕金森病最优的电极间强度的变化范围。
1、动物模型制备及鉴定
所有大鼠适应环境1星期后,采用颈背部皮下注射鱼藤酮法制备PD大鼠模型,模型组和电针治疗组给予鱼藤酮(2mg/kg,溶解于葵花油,浓度2mg/mL)颈背部皮下注射,每日1次,连续28d；正常组不做任何处理；假手术组方法同模型组,但只注射不含鱼藤酮的等量葵花油乳化液(溶剂)；电场预治疗组先对正常大鼠电场治疗7d,然后造模。造模后观察大鼠的行为学改变,参照陈忻等的行为学评分标准,对各组大鼠进行评分。评分标准如下,1分为大鼠出现拒捕行为减弱、弓背、竖毛、毛发变黄变脏、主动活动减少；2分为有1分的表现,且主动活动减少更加明显,并伴有震颤、动作迟缓、或有步态不稳；4分为有2分的表现,且步态不稳,或不能直线行走、或行走时向一侧旋转；6分为向单侧斜卧,单侧前肢或后肢瘫痪,行走困难,进食困难；8分为单侧肢体(前肢或后肢)完全瘫痪,四肢拘挛,体重大幅减轻,不能进食；10分为濒死状态或死亡。本研究在行为学评分达2～8分的大鼠中随机抽取6只大鼠以TH免疫组织化学技术作组织学鉴定。
2、电场治疗方法
大鼠造模成功后,对电场治疗各组大鼠，每只大鼠按表3治疗方案实施治疗。各组动物同步喂养。
表3：电场治疗方案
分组明细 A B C D E F G H
实施电场强度(KV) None 0.1 1 3 10 30 120 对照组
3、标本采集
造模完成后,排除死亡、行为学评分不合格(评分＜2分或＞8分)的大鼠,每组均有12只纳入标本采集。将大鼠称重后用10％水合氯醛行腹腔注射麻醉,剂量为0.2mL/100g。各组大鼠随机选取6只行左心室多聚甲醛做内固定,取大鼠中脑黑质部组织块,并用4％多聚甲醛固 定过夜,作石蜡包埋切片,用于形态学观察。另外6只大鼠待其完全麻醉后快速断头,于冰面上迅速取出脑组织并分离出中脑黑质组块,将分离的黑质组块用锡纸包裹放入液氮中速冻,然后取出组织放置在冻存管中于-80℃冰箱中保存,以备检测。
4、观察指标
(1)黑质TH、α-syn的阳性表达
采用免疫组化法检测黑质TH、α-syn的阳性表达。将上述切片进行常规脱蜡处理,切片依次放入二甲苯Ⅰ-二甲苯Ⅱ-无水乙醇Ⅰ-无水乙醇Ⅱ-95％乙醇-90％乙醇-80％乙醇-70％乙醇,然后入蒸馏水浸泡2min。采用微波进行抗原修复；用蒸馏水新鲜配置的3％H2O2滴加于切片组织上以阻断内源性过氧化物酶,PBS冲洗3次,每次3min；在显微镜观察下，用刮刀取下ROI邻域切碎后加入PBS在离心条件下提取样本，用Westernblot分别检测TH及α-syn表达程度(图4)。
None组a-syn的相对定量结果显示，相对各电场治疗组与未注射鱼藤酮法制备PD大鼠模型的各组均高(P＜0.05)，说明鱼藤酮皮下注射影响大鼠a-syn表达，且-syn数值与神经元的保护程度成反比。而TH与神经元的保护作用成正比关系，当TH处于高值时，神经元处于高度保护状态，不易感染PD。TH相对数量的变化说明鱼藤酮皮下注射影响大鼠TH表达，且TH数值与神经元的保护程度成正比。
各电场治疗组的a-syn相对定量结果高于空白组，低于None组(PD组，P＜0.05)，说明治疗后明显改善PD大鼠疾病症状，但症状恢复情况相比正常大鼠差，同时伴随治疗电场强度的增加。
各电场治疗组的TH相对定量结果低于空白组，高于None(PD组，P＜0.05)，说明治疗后神经元的保护程度得到显著改善，但症状恢复情况相比正常大鼠差，同时伴随治疗电场强度的增加。
综上所述，采用鱼藤酮注射模式，成功建立PD大鼠模型。同时TH相对数值提高，阳性细胞数量增加，a-syn含量减少；说明其对神经元的保护作用可能与保护TH及抑制a-syn表达有关。
上述实施例仅例示性说明本发明的原理及其功效，而非用于限制本发明。任何熟悉此技术的人士皆可在不违背本发明的精神及范畴下，对上述实施例进行修饰或改变。因此，举凡所属技术领域中具有通常知识者在未脱离本发明所揭示的精神与技术思想下所完成的一切等效修饰或改变，仍应由本发明的权利要求所涵盖。

Claims (10)

  1. 一种神经系统疾病治疗电场的发生装置，其特征在于，所述发生装置至少包括：
    空间电场接触电极；
    电极头盔，所述电极头盔为一端开口的中空腔体，所述电极头盔内壁设有空间电场外电极，所述空间电场外电极用于与所述空间电场接触电极之间形成空间电场，所述空间电场外电极包括2个以上异电极；各个异电极的位置可调，用于调整空间电场的覆盖面积。
  2. 根据权利要求1所述的神经系统疾病治疗电场的发生装置，其特征在于：还包括以下特征中的一项或多项：
    1)所述空间电场接触电极用于与待测对象相连接，使待测对象与所述空间电场接触电极形成等电位；
    2)所述空间电场接触电极接地；
    3)所述发生装置还包括：
    供电电源，用于给所述发生装置提供电能；
    调控单元，用于调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场范围中的一种或多种；
    4)所述异电极为点状探头；
    5)所述异电极的排布方式选自点阵排布，为2 n点阵，其中n为非0自然数；
    6)所述电极头盔为绝缘材料制成；
    7)所述电极头盔的空腔为半球形空腔。
  3. 根据权利要求2所述的神经系统疾病治疗电场的发生装置，其特征在于，还包括以下特征中的一项或多项：
    1)特征1)中，所述空间电场接触电极与待检测对象之间通过水作为导电接触；
    2)特征1)中，所述电极头盔不与待检测对象接触；
    3)特征3)中，所述异电极的位置和/或空间电场的性能根据其他诊断数据确认；和/或，所述异电极的位置、数量和/或空间电场性能根据电场耦合电流诊断后自动跟踪调整；
    4)特征3)中，所述供电电源为高压输出电源；
    5)特征3)中，所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm。
  4. 一种空间电场的发生方法，至少包括以下步骤：
    1)使空间电场接触电极接触生物活体；
    2)将电极头盔置于所述生物活体的头部上方；
    3)调节空间电场外电极的2个以上异电极的位置，用于调整空间电场的覆盖面积；
    4)将所述空间电场接触电极及所述空间电场外电极接通电源，产生空间电场。
  5. 根据权利要求4所述的空间电场的发生方法，其特征在于，还包括调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场点阵范围中的一种或多种。
  6. 根据权利要求4所述的空间电场的发生方法，其特征在于，所述发生方法还包括以下特征中的一个或多个：
    1)所述空间电场接触电极接地；
    2)所述异电极为点状探头；
    3)所述异电极的排布方式选自点阵排布，为2 n点阵，其中n为非0自然数；
    4)所述空间电场接触电极与生物活体之间通过水作为导电接触；
    5)所述电极头盔不与生物活体接触；
    6)所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm。
  7. 根据权利要求1-3任一所述的神经系统疾病治疗电场的发生装置的使用方法，其特征在于，所述方法至少包括如下步骤：
    1)将待检测对象空间电场接触电极连接，使待测对象与所述空间电场接触电极形成等电位；
    2)将电极头盔置于所述待检测对象的上方；
    3)调整各个异电极的位置，以调整空间电场的覆盖面积。
  8. 根据权利要求7所述的神经系统疾病治疗电场的发生装置的使用方法，其特征在于，所述使用方法还包括以下特征中的一个或多个：
    1)所述空间电场接触电极接地；
    2)所述异电极为点状探头；
    3)所述异电极的排布方式选自点阵排布，为2 n点阵，其中n为非0自然数；
    4)所述空间电场接触电极与待检测对象之间通过水作为导电接触；
    5)所述电极头盔不与待检测对象接触；
    6)所述供电电源的电压为可调的0.001kV-120kV，电流输出为可调的0.001mA-10000mA，电场的工作距离为可调的0.1cm-100cm。
    7)所述使用方法还包括以下步骤：
    调节控制空间电场的性能，包括电场强度、电场方向、电场脉冲频率以及电场范围中的一 种或多种。
  9. 根据权利要求8所述的神经系统疾病治疗电场的发生装置的使用方法，其特征在于，特征7)中，所述异电极的位置和/或空间电场的性能根据其他诊断数据确认；和/或，所述异电极的位置、数量和/或空间电场性能根据电场耦合电流诊断后自动跟踪调整。
  10. 如权利要求1-3任一所述的神经系统疾病治疗电场的发生装置或权利要求4-6任一所述的空间电场的发生方法在神经元传输电子过程干预中的用途。
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