CN118286595A - Analysis method for radio stimulation targeted repair of spinal cord injury - Google Patents
Analysis method for radio stimulation targeted repair of spinal cord injury Download PDFInfo
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- Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
Abstract
The invention relates to an analysis method for repairing spinal cord injury by radio stimulation in a targeted manner, a spinal cord injury model is constructed by cutting off specific spinal cord segments on a C57 mouse through a surgical operation, BBB function scoring is carried out on the C57 mouse after modeling to realize the behavioral observation of spinal cord injury, and then application research of a micron-sized battery-free electric stimulation device is carried out on the C57 mouse after modeling, so that the physiological capability change of the model under electric stimulation is observed. The invention proposes that the electrical stimulation has positive effect on the recovery of spinal cord injury.
Description
Technical Field
The invention relates to an analysis method for repairing spinal cord injury by radio stimulation in a targeted manner, and research on recovery of motor functions after spinal cord injury by electric stimulation. The invention also provides device design and dose optimization for repairing spinal cord injury in a targeted manner by using the electrical stimulation in future clinical application. The invention belongs to the fields of biomedical engineering and the like.
Background
Spinal cord injury (spinal cord injury, SCI) is caused by external indirect or direct factors to cause the displacement of vertebral bodies or the protrusion of broken bone fragments in vertebral canal, so that spinal cord or cauda equina nerves are damaged to different degrees, and then the motor, sense, sphincter, reflex and other functions of a damaged plane are blocked, and at the moment, the patient may be paralyzed or even dead. So far, spinal cord injury is limited by the specificity of injury sites, the local microenvironment of injury is unfavorable for nerve cell regeneration, the serious medical problem which is not solved in the world still exists, no effective treatment method exists in clinic at home and abroad at present, and the diseases seriously threaten the health and daily life of people in China. Therefore, more scientific and effective repair or treatment of spinal cord injury is a current urgent problem.
In recent years, methods for promoting regeneration of tissues such as blood vessels and nerve cells to repair spinal cord injury by physical methods such as light, electricity, magnetism and ultrasound are widely paid attention to doctors and scholars at home and abroad. Among them, electrical stimulation (ELECTRICAL STIMULATION, ES) is becoming increasingly popular as a targeted therapy after spinal cord injury, and in experimental models of the intact and injured central nervous system, electrical stimulation has been shown to affect continuous changes in connectivity and synaptic strength of the stimulated pathway. The main principle of ES is to overcome the axon growth inhibitor near the SCI site by electrically activating to influence the growth of neurons and by its influence on the expression of growth factors such as BDNF and endogenous second messengers such as cAMP. Studies have shown that increasing intracellular neuronal cAMP and BDNF levels by ES even before injury has been demonstrated to enhance axonal growth following spinal cord injury, cells are considered to be in a growth-promoting readiness state when injury does occur. In conclusion, targeting ES in the nervous system following SCI promotes regeneration of tissue such as nerve cells, making ES an important tool for repairing spinal cord injury.
However, there are many limitations to the ES systems currently used for spinal cord injury repair. First, and most importantly, the power supply limitation, since most implantable stimulators require a battery as a power source, the power supply battery occupies more than 80% of the total size of the implantable device, and thus, targeting of ES to spinal cord injury is poor, thereby affecting therapeutic efficacy. In addition, battery powered stimulators require a second surgical procedure to replace the battery every few years, which may reduce the therapeutic effect and increase additional risks.
Therefore, in order to further solve the problems, and simultaneously realize more accurate regulation and control of deep tissues of the spinal cord and better targeted electrical stimulation treatment effect, the invention provides feasibility of research on a model for targeted repair of spinal cord injury by a battery-free inductively coupled power supply type micron-sized electrical stimulator.
Disclosure of Invention
The invention provides an analysis method for repairing spinal cord injury by radio stimulation in a targeted manner, which is significant for researching that the motor function is recovered after spinal cord injury by electric stimulation.
The technical scheme of the invention is as follows:
and constructing a spinal cord injury model by surgically resecting a specific spinal cord segment of the C57 mouse, performing BBB function scoring on the C57 mouse after modeling, performing spinal cord injury behavioural observation, and then performing application research of implanting a micron-sized battery-free power-supply type electric stimulation device on the C57 mouse to observe the physiological capability change of the model under electric stimulation.
The specific method comprises the following steps:
(1) Construction of spinal cord injury model
The invention adopts specific spinal segment of the excised C57 mouse to construct a spinal cord injury model, and the spinal cord injury model formed in the mode is widely accepted at present. Normal healthy mice were weighed and anesthetized prior to the experiment. After fixing the mouse, shaving and simply sterilizing the dorsal hair of the incision part of the mouse, cutting the back skin of the 11 th to 12 th vertebrae of the mouse after the treatment is finished, finding the 2 nd to 3 rd spinous processes of the back of the C57 mouse, longitudinally cutting an incision by using a surgical knife until subcutaneous tissues are exposed, stripping the muscles on two sides of the spinous processes and the ligaments between the 2 nd to 3 rd spinous processes of the incision part by using a blunt force divider to expose the spinal cord, cutting the spinal cord after finding the spinal cord, and taking out part of the spinal cord by using surgical forceps to damage the part of the spinal cord. Finally, the cut external skin of the mice was sutured using a suture needle to obtain the desired model of spinal cord injury in the C57 mice.
(2) Postoperative care
After operation, the state of the experimental mouse needs to be closely observed, the urination and defecation states of the experimental C57 mouse are observed, meanwhile, the back operation wound part of the modeling mouse is observed, and whether malignant phenomena such as infection, bleeding and the like exist at the part is observed. The modeled mice were subcutaneously injected daily with ceftriaxone sodium (5 ug/g) for one week post-surgery to prevent infection. Because the model mouse is paralyzed down, the artificial urination is needed, during the experiment, the urine is needed to be drained by squeezing the bladder in time every day, and the urine is needed to be drained twice a day by squeezing the bladder once in the morning and evening.
(3) Behavioural observation of spinal cord injury in mice
In the invention, by means of an animal science monitoring device, a video real-time monitoring and recording method is adopted to study the differential effect of the behavior of the mice before and after spinal cord injury. In scoring, the experimental animal is placed in a washtub with the diameter of about 50cm or other containers with little influence on the scoring result after the experimental animal is allowed to be considered, the scoring personnel can tap the tub wall to creep the mice at one side and score the animals according to coordination of joints such as buttocks, knees and ankles and other activity standards of BBB scoring when the animals act. From the initial stage of spinal cord injury, 8 weeks later, it can be seen that mice are self-repairing after spinal cord injury. The mice began to recover from spinal cord injury and recovered substantially to the best state that they recovered after the second week, but by scoring, spontaneous recovery was not sufficient to restore the hindlimb motor ability of the mice to that of normal mice.
(4) Analysis of the effect of electrical stimulation on a model
The invention constructs a spinal cord injury charged stimulation electrode model, which can be divided into two parts, wherein one part is a C57 mouse spinal cord injury model, and the other part is to embed a front-end wireless electric stimulator into a damage part when a spinal cord injury link is generated in the spinal cord injury model construction, and to apply an electromagnetic field to the implanted stimulator to perform electric stimulation. In the present invention, the motor function of the C57 mice after receiving the electric stimulation is significantly stronger than that of the C57 mice which do not receive the electric stimulation at the same time. And the recovery degree is higher and higher with the passage of time, and the influence and treatment of the electric stimulation on the spinal cord injury of the mice are obvious.
(5) Feasibility verification scheme after implantation of electrical stimulation
In the invention, after the micron-sized radio stimulation device is implanted into a target position, an electromagnetic field is applied to an implanted stimulator to perform stimulation test, an external coil composes a signal mode through a signal generator, and a magnetic field is generated after the signal mode is amplified through a power amplifier, so that the implanted radio stimulation device is further driven to work. To test the force generated by muscle contraction caused by stimulus by placing an accelerometer at the toe end of the mouse to capture motion, a moment measuring tool is used, the line of the moment sensor is passed through the pulley system on the ankle of the mouse to detect the force as a function of voltage, and the measured force is digitized and stored in a computer for further analysis. Sufficient rest is given between the test sections to avoid muscle fatigue caused by electrical stimulation.
Drawings
FIG. 1 is a schematic diagram of the structural design of an implantable micron-sized battery-less powered electrostimulation device;
Fig. 2 is a schematic diagram of an implantable electrical stimulation feasibility verification scheme.
Detailed Description
The invention describes an analysis method for repairing spinal cord injury by targeting radio stimulation, which is designed to perform targeted electric stimulation at the spinal cord injury place, and introduces the preparation of a spinal cord injury model, postoperative care of experimental mice, behavioral observation of spinal cord injury of mice, influence analysis of electric stimulation on the model and feasibility verification scheme after electric stimulation implantation in detail.
Claims (6)
1. The analysis method for the radio stimulation targeted repair of the spinal cord injury is characterized by comprising the specific experiments and analysis methods of constructing a spinal cord injury model, performing postoperative care, performing behavioral observation on the spinal cord injury of a mouse, analyzing the influence of the electric stimulation on the model and performing feasibility verification scheme after the electric stimulation implantation.
2. The method of claim 1, wherein the step of constructing the spinal cord injury model is performed by surgically resecting a specific spinal cord segment from a C57 mouse to construct the spinal cord injury model from the C57 mouse, wherein the model can be recorded and observed in real time during behavioral observations.
3. The postoperative care according to claim 1, wherein the state of the experimental mice is closely observed after the operation, the urination and defecation states of the experimental C57 mice are observed, the model mice are paralyzed down, the urination is assisted by squeezing the bladder in time every day, and the artificial urination is needed twice a day.
4. The behavioral observation of spinal cord injury in mice according to claim 1, wherein in the present invention, the differential effect of the behavioral before and after spinal cord injury in mice is studied by means of an animal monitoring device using a video real-time monitoring recording method, while using BBB function scoring.
5. The analysis of the effect of electrical stimulation on the model according to claim 1, wherein a front-end radio stimulator is embedded in the injured site when constructing the spinal cord injury live stimulation electrode model, wherein the electrical stimulator is a micron-scale electromagnetic inductive coupling power supply type radio nerve stimulator which can provide enough current to target and stimulate the peripheral nerve of the spinal cord injury site, and for realizing more accurate targeted electrical stimulation, a very simple front-end circuit design is adopted, and the front-end stimulation device only comprises: one inductor L is responsible for receiving power, one shunt capacitor C 1 for facilitating rectification, one capacitor C 2 is responsible for resonant inductor and one schottky diode D 1 for rectification.
6. The post-implantation feasibility verification scheme of claim 1, wherein after the micron-sized radio stimulation device is implanted at the target site, the stimulation test is performed by applying an electromagnetic field to the implanted stimulator, the external coil composes a signal pattern through the signal generator, and the magnetic field is generated after the signal pattern is amplified through the power amplifier, so as to further drive the operation of the implanted radio stimulation device; capturing motion by placing an accelerometer at the toe end of the mouse; the force generated by the muscle contraction caused by the stimulus was tested on the ankle of the mouse by passing the line of the torque sensor through the pulley system using a torque measuring tool.
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| CN202410342102.5A CN118286595A (en) | 2024-03-25 | 2024-03-25 | Analysis method for radio stimulation targeted repair of spinal cord injury |
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| CN202410342102.5A CN118286595A (en) | 2024-03-25 | 2024-03-25 | Analysis method for radio stimulation targeted repair of spinal cord injury |
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