Physical methods and devices for modulating molecular transport in the extracellular space of the brain

Abstract

A physical method for regulating molecular transport in the extracellular space of the brain includes applying an external pressure to the brain tissue of an animal, and the rhythm of applying the external pressure is associated with the automaticity of the animal. A device for regulating molecular transport in the extracellular space of the brain includes a detection mechanism, a pressure mechanism, and a control mechanism. The detection mechanism is capable of detecting the automaticity of the animal. The pressure mechanism is capable of applying an external pressure to the brain tissue of the animal. The control mechanism is capable of controlling the pressure mechanism based on the detection result of the detection mechanism such that the rhythm of applying the external pressure of the pressure mechanism is associated with the automaticity of the animal. The method and device can effectively regulate molecular transport in the extracellular space of the brain.

Description

[Technical field]

[0001] The present patent relates to physical methods and devices for modulating molecular transport in the extracellular space of the brain. [Background technology]

[0002] The extracellular space (ECS) of the brain is a tortuous space that exists between brain cells and between cells and blood vessels, and there are two modes of material transport in this space: convection and diffusion. The novel administration method via the ECS route successfully circumvents the blood-brain barrier that prevents most drugs from entering the brain, and offers new hope for many drugs that have failed in research and development via traditional oral and intravenous administration routes.

[0003] The factors influencing substance transport in the ECS are complex, and both nerve excitation and the release of transmitters after excitation cause changes in the substance transport rate in the ECS (Y. Li et al., 2020; Shi et al., 2015). Various factors such as sleep (Xie et al., 2013), anesthesia (Zhao et al., 2020), nerve excitation (Shi et al., 2015), and development (R. Wang et al., 2021) may all exert forward or reverse control on the drainage of brain tissue interstitial fluid (ISF) in the brain ECS. All of these provide important theoretical foundations and technical methods for exploring the treatment of stroke via the ECS pathway. For example, pain stimulation (Shi et al., 2015), olfactory stimulation can slow down the ISF drainage rate, light exposure can treat Alzheimer's disease (AD) by speeding up ISF drainage and promoting the exit of abs from the brain (Yue et al., 2019), and different days of simulated weightlessness (Gao et al., 2021) and different anesthesia types (Zhao et al., 2020) can control ISF drainage in the forward or reverse direction.

[0004] Currently, there is a need for more effective methods of modulating molecular transport in the extracellular space of the brain. Summary of the Invention [Problem to be solved by the invention]

[0005] It is an object of the present invention to provide a novel method by which molecular transport in the extracellular space of the brain can be effectively regulated.

[0006] Another object of the present invention is to provide a device that can effectively regulate molecular transport in the extracellular space of the brain. [Means for solving the problem]

[0007] The physical method of regulating molecular transport in the extracellular space of the brain according to the present invention comprises applying external pressure to the brain tissue of an animal, the rhythm of the application of the external pressure being associated with the motility of the animal.

[0008] The physical methods for modulating molecular transport in the extracellular space of the brain can effectively modulate molecular transport in the extracellular space of the brain.

[0009] In another exemplary embodiment of the physical method of regulating molecular transport in the extracellular space of the brain, the automaticity is respiratory rhythm, cardiac rhythm, brain pulsation rhythm or vascular pulsation rhythm.

[0010] In yet another exemplary embodiment of a physical method for modulating molecular transport in the extracellular space of the brain, external pressure is applied to the brain tissue of the animal outside the dura mater of the animal.

[0011] The device for regulating molecular transport in the extracellular space of the brain according to the present invention includes a detection mechanism, a pressure mechanism, and a control mechanism. The detection mechanism can detect the motility of an animal. The pressure mechanism can apply an external pressure to the brain tissue of the animal. The control mechanism can control the pressure mechanism based on the detection result of the detection mechanism so that the rhythm of applying the external pressure of the pressure mechanism is related to the motility of the animal. The device for regulating molecular transport in the extracellular space of the brain can effectively regulate molecular transport in the extracellular space of the brain by a physical method.

[0012] In another exemplary embodiment of the device for regulating molecular transport in the extracellular space of the brain, the automaticity is respiratory rhythm, cardiac rhythm, brain pulsation rhythm or vascular pulsation rhythm.

[0013] In yet another exemplary embodiment of the device for regulating molecular transport in the extracellular space of the brain, the pressurizing mechanism includes a flexible bag, a fluid container, and a fluid filling and discharging unit. The flexible bag is filled with a fluid, thereby applying an external pressure to the animal's brain tissue. The fluid container stores a fluid. The fluid filling and discharging unit is connected to the flexible bag and the fluid container, and is capable of filling the flexible bag with the fluid stored in the fluid container and discharging the fluid in the flexible bag. The control mechanism is capable of controlling the fluid filling and discharging unit.

[0014] In yet another exemplary embodiment of the device for regulating molecular transport in the extracellular space of the brain, the detection mechanism is an electrocardiograph, the control mechanism is capable of extracting QRS waves and T waves from the detection results of the detection mechanism, and the control mechanism is capable of controlling the fluid filling and discharging unit to fill the flexible bag with fluid at the start of the QRS wave and to discharge the fluid from the flexible bag at the end of the T wave.

[0015] In yet another exemplary embodiment of the device for regulating molecular transport in the extracellular space of the brain, the fluid filling and exhausting unit includes an intake tube, a gas compressor, an exhaust tube, and an exhaust valve. The intake tube is connected at one end to the flexible bag and at the other end to the outlet of the gas compressor. The inlet of the gas compressor is connected to a fluid container. The exhaust tube is connected at one end to the flexible bag and at the other end to the exhaust valve. The control mechanism is capable of controlling the gas compressor and the exhaust valve.

[0016] In yet another exemplary embodiment of the device for modulating molecular transport in the extracellular space of the brain, the fluid charging and discharging unit further includes an intake valve disposed between the gas compressor and the fluid container.

[0017] In yet another exemplary embodiment of the device for regulating molecular transport in the extracellular space of the brain, the fluid filling and discharging unit further includes a flow meter connected to the control mechanism. The flow meter is provided in the intake pipe and the exhaust pipe to detect the volume of fluid flowing through the intake pipe and the exhaust pipe. The control mechanism can integrate the total intake volume and / or the total exhaust volume based on the detection result of the flow meter. The device further includes a display unit connected to the control mechanism, and the control mechanism can control the display unit to display the detection result of the detection mechanism, the total intake volume and / or the total exhaust volume.

[0018] In yet another exemplary embodiment of the device for modulating molecular transport in the extracellular space of the brain, the pressure mechanism includes a motor and a pressure plate. The control mechanism is capable of controlling the operation of the motor. The pressure plate is connected to an output end of the motor, and the motor is capable of driving the pressure plate to move and apply external pressure to the brain tissue of the animal.

[0019] In yet another exemplary embodiment of the device for regulating molecular transport in the extracellular space of the brain, the device further includes a pressure sensor that is provided in the pressurizing mechanism and detects the pressure applied from the pressurizing mechanism to the brain tissue. The pressure sensor is connected to the control mechanism, and the control mechanism is capable of controlling the pressurizing mechanism based on the detection result of the pressure sensor so that the maximum value of the external pressure applied from the pressurizing mechanism to the animal's brain tissue meets a set value.

[0020] In yet another exemplary embodiment of the device for modulating molecular transport in the extracellular space of the brain, the device further includes an input mechanism connected to the control mechanism and capable of inputting operating parameters and on-off signals to the control mechanism by the input mechanism, the operating parameters including a maximum set value for the external pressure applied to the animal's brain tissue by the pressure applying mechanism.

[0021] The following drawings are merely illustrative and explanatory of the present invention and are not intended to limit the scope of the present invention. [Brief description of the drawings]

[0022] [Figure 1] FIG. 1 is a schematic diagram illustrating an exemplary embodiment of a device for modulating molecular transport in the extracellular space of the brain. [Diagram 2] FIG. 1 is a schematic diagram illustrating an exemplary embodiment of a device for modulating molecular transport in the extracellular space of the brain. [Diagram 3] FIG. 2 is a schematic diagram of the pressurizing mechanism of the device for regulating molecular transport in the extracellular space of the brain shown in FIG. 1. [Figure 4A] This is a nuclear magnetic resonance scan image from an effect experiment. [Figure 4B] This is a nuclear magnetic resonance scan image from an effect experiment. [Figure 4C] This is a nuclear magnetic resonance scan image from an effect experiment. [Figure 4D] This is a nuclear magnetic resonance scan image from an effect experiment. [Diagram 5] 13 is a histogram of feature values ​​of brain ECS structures in the effect experiment. [Figure 6] 13 is a histogram of feature values ​​of brain ECS structures in the effect experiment. [Figure 7] 13 is a histogram of feature values ​​of brain ECS structures in the effect experiment. [Figure 8] 13 is a histogram of feature values ​​of brain ECS structures in the effect experiment. [Figure 9A] FIG. 2D diagram reflecting molecular diffusion coefficients in the brain ECS. [Figure 9B] FIG. 2D diagram reflecting molecular diffusion coefficients in the brain ECS. [Figure 9C] FIG. 2D diagram reflecting molecular diffusion coefficients in the brain ECS. [Figure 9D] FIG. 2D diagram reflecting molecular diffusion coefficients in the brain ECS. [Figure 10A] FIG. 2 is a three-dimensional diagram reflecting molecular diffusion coefficients in the brain ECS. [Figure 10B] FIG. 2 is a three-dimensional diagram reflecting molecular diffusion coefficients in the brain ECS. [Figure 10C] FIG. 2 is a three-dimensional diagram reflecting molecular diffusion coefficients in the brain ECS. [Figure 10D] FIG. 2 is a three-dimensional diagram reflecting molecular diffusion coefficients in the brain ECS. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0023] In order to make the technical features, objects and effects of the invention more clearly understandable, specific embodiments of the present invention will be described with reference to the drawings, in which the same reference numerals denote elements that are the same or similar in structure but have the same function.

[0024] As used herein, "exemplary" means "serving as an example, instance, or illustration," and any illustration or embodiment described herein as "exemplary" is not to be construed as a preferred or more advantageous technical solution.

[0025] For the sake of simplicity, each drawing shows only parts related to the present invention, but does not represent the actual structure of the product.

[0026] 1 is a schematic diagram illustrating an exemplary embodiment of the device for regulating molecular transport in the extracellular space of the brain. As shown in FIG. 1, the device for regulating molecular transport in the extracellular space of the brain includes a detection mechanism 10, a pressure mechanism 30, and a control mechanism 50.

[0027] The detection mechanism 10 can detect the automaticity of an animal. With regard to automaticity (abbreviated as automaticity), generally, when a certain system is active without an external stimulus, this system has automaticity, and in physiology, automaticity generally refers to a part or organ of a living body being able to continue an exciting activity without another stimulus. The automaticity of an animal is, for example, a breathing rhythm, a heartbeat, a brain pulsation rhythm, or a blood vessel pulsation rhythm. When the automaticity is a heartbeat, the detection mechanism 10 is, for example, an electrocardiograph.

[0028] The pressurizing mechanism 30 can apply an external pressure to the brain tissue of an animal. The external pressure refers to a force applied to the brain tissue from a structure other than the brain tissue. FIG. 3 is a schematic diagram of a specific structure of the pressurizing mechanism. Specifically, as shown in FIG. 3, in this exemplary embodiment, the pressurizing mechanism 30 includes a flexible bag 31, a fluid container 32 for storing a fluid, and a fluid filling and discharging unit 33. The flexible bag 31 can apply an external pressure to the brain tissue of an animal by being filled with a fluid. As shown in FIG. 1 and FIG. 2, in use, the flexible bag 31 is disposed, for example, between the skull 91 and the dura mater 92 of the animal, but is not limited thereto, and in other uses, the flexible bag 31 may be disposed, for example, on the side of the dura mater 92 of the animal that is away from the skull 91. The flexible bag 31 is, for example, manufactured from a polymer polyurethane material, has good flexibility, is dimensioned to be disposed between the skull 91 and the dura mater 92, and is set to be as thin as possible. FIG. 1 shows a state after the fluid is discharged from the flexible bag 31, and FIG. 2 shows a state in which the flexible bag 31 is filled with fluid and pressure is applied to the brain tissue. The fluid is, for example, a gas, and the gas is, for example, helium gas. In other exemplary embodiments, the fluid may be a liquid. The fluid filling and discharging unit 33 is connected to the flexible bag 31 and the fluid container 32. The fluid filling and discharging unit 33 can fill the flexible bag 31 with the fluid stored in the fluid container 32. The fluid filling and discharging unit 33 can also discharge the fluid in the flexible bag 31. In the exemplary embodiment, the fluid container 32 is, for example, a high-pressure gas storage tank.

[0029] 3, in this exemplary embodiment, the fluid filling and discharging unit 33 includes, for example, an intake pipe 331, a gas compressor 332, an exhaust pipe 333, and an exhaust valve 334. One end of the intake pipe 331 is connected to the flexible bag 31. The gas compressor 332 has an outlet connected to the other end of the intake pipe 331 and an inlet connected to the fluid container 32. One end of the exhaust pipe 333 is connected to the flexible bag 31. The exhaust valve 334 is connected to the other end of the exhaust pipe 333, and the exhaust valve 334 is, for example, an electromagnetic valve.

[0030] The control mechanism 50 can control the pressurizing mechanism 30 such that the rhythm of applying external pressure by the pressurizing mechanism 30 is associated with the automaticity of the animal based on the detection result of the detection mechanism 10. Specifically, in this exemplary embodiment, the control mechanism 50 can control the fluid charging and discharging unit 33, and further, the control mechanism 50 can control the gas compressor 332 and the exhaust valve 334.

[0031] The device for regulating molecular transport in the extracellular space of the brain is capable of applying external pressure to the brain tissue of an animal, and the rhythm of applying the external pressure is associated with the motility of the animal.

[0032] In the exemplary embodiment, the fluid filling and discharging unit 33 further includes an intake valve 336 disposed between the gas compressor 332 and the fluid container 32 .

[0033] In this exemplary embodiment, the detection mechanism 10 is, for example, an electrocardiograph, and the control mechanism 50 can extract, for example, a QRS wave and a T wave from the detection result of the detection mechanism 10. The control mechanism 50 can control the fluid filling and discharging unit 33 to fill the flexible bag 31 with fluid at the start point of the QRS wave, and can control the fluid filling and discharging unit 33 to discharge the fluid from the flexible bag 31 at the end point of the T wave. This is advantageous for accurate control. Specifically, in this exemplary embodiment, the control mechanism 50 includes, for example, a preamplifier 51, a high-pass filter 52, a pulse amplitude and frequency extraction circuit 53, and a microcontroller 54. The electrocardiogram signal measured by the electrocardiograph enters the pulse amplitude and frequency extraction circuit 53 after the baseline is removed by the preamplifier 51 and the high-pass filter 52, and is shaped into a digital pulse in the pulse amplitude and frequency extraction circuit 53 and transmitted to the microcontroller 54, and the microcontroller 54 can control the exhaust valve 334 and the intake valve 336.

[0034] 3, in the exemplary embodiment, the fluid charging and discharging unit 33 further includes a flow meter 335. The flow meter 335 is provided in the intake pipe 331 and the exhaust pipe 333 to detect the volume of fluid flowing through the intake pipe 331 and the exhaust pipe 333. The flow meter 335 is connected to the control mechanism 50. The control mechanism 50 can integrate the total intake amount and / or the total exhaust amount based on the detection result of the flow meter 335. This makes it easier for the user to monitor the operating status of the device.

[0035] 1, in an exemplary embodiment, the device for regulating molecular transport in the extracellular space of the brain further includes a display unit 60 connected to the control mechanism 50. The control mechanism 50 can control the display unit 60 to display the detection result of the detection mechanism 10, the total intake volume, the total exhaust volume, etc., to facilitate the user to monitor the operation status of the device.

[0036] As shown in FIG. 1, in an exemplary embodiment, the device for regulating molecular transport in the extracellular space of the brain further includes a pressure sensor 70 that is provided in the pressurizing mechanism 30 and detects the pressure applied from the pressurizing mechanism 30 to the brain tissue. The pressure sensor 70 is connected to the control mechanism 50. Based on the detection result of the pressure sensor 70, the control mechanism 50 can control the pressurizing mechanism 30 so that the maximum value of the external pressure applied from the pressurizing mechanism 30 to the brain tissue of the animal satisfies a set value. This makes it easier to control the magnitude of the applied pressure.

[0037] As shown in FIG. 1, in an exemplary embodiment, the device for regulating molecular transport in the extracellular space of the brain further includes an input mechanism 80 connected to the control mechanism 50. The input mechanism 80 allows operation parameters and on-off signals to be input to the control mechanism 50, and the operation parameters include a maximum setting value of the external pressure applied to the animal's brain tissue from the pressure mechanism 30. The input mechanism 80 is, for example, a key. However, without being limited thereto, in other exemplary embodiments, the input mechanism 80 may be, for example, a knob or a touch mechanism (e.g., a touch keyboard). This makes it easier for the user to control the device.

[0038] In an exemplary embodiment, the device for modulating molecular transport in the extracellular space of the brain further comprises a battery to provide the electrical energy required for operation.

[0039] In other exemplary embodiments, the pressure mechanism may further include, for example, a motor and a pressure plate. The control mechanism may control the operation of the motor. The pressure plate is connected to an output end of the motor, and the motor may drive the pressure plate to move and apply external pressure to the animal's brain tissue. However, without being limited thereto, the pressure mechanism may be other structures capable of applying external pressure to the animal's brain tissue.

[0040] Hereinafter, an experiment will be conducted to verify the effect on molecular transport in the extracellular space of the brain of applying external pressure to the brain tissue of an animal, where the rhythm of the applied external pressure is associated with the automaticity of the animal.

[0041] Effect experiment In this experiment, external pressure was applied to the rat's brain tissue using the rat's own arterial pulsation so that the rhythm of the applied external pressure was the same as the arterial vascular pulsation rhythm.

[0042] According to the experimental requirements, the rats were randomly divided into four groups. Control group (group A): No arterial patch was performed. Arterial patching group (group B): Arterial patching was performed and ipsilateral contrast medium was injected. Contralateral arterial patching group (group C): arterial patching was performed and contralateral contrast medium was injected. Group D: Arterial patch followed by gelatin sponge pad was applied, and the arterial patch was administered, ipsilateral contrast medium was injected, and gelatin sponge was applied.

[0043] 1. Treatment of experimental animals Arterial attachment: An artery of the rat was attached to the right brain epidural space. Ipsilateral contrast: The contrast is present in the right caudate nucleus of the rat. Contralateral contrast: Contrast is present in the left caudate nucleus of the rat. Gelatin sponge patch: To suppress the effects of arterial pulsation, a gelatin sponge is placed under the artery of the arterial patch.

[0044] 2. Nuclear magnetic resonance scanning and data post-processing The rats were placed in a prone position and subjected to a nuclear magnetic resonance scan, and images were collected until the diffusion of the contrast agent was complete. The collected images are shown in Figure 4A, Figure 4B, Figure 4C, and Figure 4D, which correspond to groups A, B, C, and D, respectively. In the figures, Cor: coronal image of the rat brain, Axi: axial image of the rat brain, Sag: sagittal image, Pre: image without contrast agent, and 15 to 240 min: time point of image collection.

[0045] The results of the nuclear magnetic resonance scans were post-processed using NanoDetect analysis software to obtain the parameters of the contrast agent half-life (T1 / 2), the molecular diffusion coefficient in the brain ECS (D*), the tortuosity of the brain ECS (λ), and the volume fraction of the brain occupied by the brain ECS (α). The results are shown in Figures 5, 6, 7, and 8, respectively.

[0046] 3.Result analysis As shown in Figures 4A-4D, the contrast agent diffuses to the ipsilateral superficial cortex in the caudate nucleus region. The bright white contrast agent spots in Figures 4A-4D disappear at essentially the same rate, which is likely due to the insufficient resolution of the nuclear magnetic images.

[0047] As can be seen from Figures 5 to 8, the arterial patch group (group B) had a shorter contrast half-life (T1 / 2), a higher molecular diffusion coefficient (D*) in the brain ECS, a smaller tortuosity (λ) of the brain ECS, and a higher volume fraction (α) of the brain occupied by the brain ECS compared to the other groups on the 1st, 3rd, 7th, and 15th days. As can be seen from these figures, arterial patching can speed up ISF drainage in rat brain tissue, increase the diffusion of micromolecules, reduce the tortuosity, and expand the occupancy rate of the brain ECS space. However, the arterial patch contralateral group (group C) and the arterial patch gelatin sponge pad group (group D) showed no statistical difference compared to the above parameters of the control group (group A).

[0048] The conclusion that arterial patching can enhance the molecular diffusion coefficient in the brain ECS is also evident from the D-mapping visualization graph of the molecular diffusion coefficient in the brain ECS. Figures 9A, 9B, 9C, and 9D are two-dimensional diagrams reflecting the molecular diffusion coefficient in the brain ECS, corresponding to groups A, B, C, and D, respectively. Figures 10A, 10B, 10C, and 10D are three-dimensional diagrams reflecting the molecular diffusion coefficient in the brain ECS, corresponding to groups A, B, C, and D, respectively. The color distribution in Figures 9A to 9D and the height of the three-dimensional columns in Figures 10A to 10D both reflect the magnitude of the molecular diffusion coefficient in the brain ECS. As shown in the figures, the arterial patching group (group B) has the highest molecular diffusion coefficient in the brain ECS compared to the other three groups, i.e., the strongest molecular diffusion ability in the brain ECS.

[0049] 4. Experimental conclusions According to the above experimental results, compared with the control group (group A), the cerebral ISF drainage of rats in the arterial patching group (group B) was accelerated, and such a change was detected on the first day after surgery and continued until the 15th day. However, no obvious difference was observed in the contralateral arterial patching group (group C), which indicates that the arterial patching can effectively improve ISF drainage from the deep part of the ipsilateral brain to the brain surface for a long time, while no obvious improvement was observed in the ISF drainage of the contralateral brain, indicating that it has the effect of regional control.

[0050] According to the above experimental results, the cerebral ISF drainage of the gelatin sponge pad group (group D) after arterial patching was not significantly different from that of the control group (group A), that is, after suppressing the influence of arterial pulsation, the cerebral ISF drainage returned to normal. As can be seen from the results of Figures 5 to 10, the arterial patching can increase the cerebral ISF drainage rate, increase the cerebral ECS space occupancy rate, reduce the tortuosity rate, and enhance the molecular diffusion ability.

[0051] This indicates that epidural arterial attachment can promote molecular diffusion in the brain ECS and change the structure of the brain ECS.

[0052] In the above-mentioned effect experiment, the rat's own arterial pulsation is used to apply external pressure to the rat's brain tissue, but instead of the arterial pulsation, the device for regulating molecular transport in the extracellular space of the brain shown in Figure 1 is used to apply external pressure to the rat's brain tissue, and the rhythm of applying external pressure is made the same as the vascular pulsation rhythm of the animal's artery, thereby achieving the same effect as the arterial patching group (group B) in the above-mentioned effect experiment, that is, it should be understood that the brain ISF drainage rate is accelerated, the brain ECS space occupancy rate is increased, the tortuosity rate is reduced, and the molecular diffusion capacity is enhanced. The device for regulating molecular transport in the extracellular space of the brain can effectively regulate molecular transport in the extracellular space of the brain.

[0053] The physical method for regulating molecular transport in the extracellular space of the brain according to the present invention includes applying external pressure to the brain tissue of an animal, and the rhythm of applying the external pressure is associated with the automaticity of the animal. The automaticity is, for example, respiratory rhythm, heartbeat, brain pulsation rhythm, or vascular pulsation rhythm. The site to which the external pressure is applied is, for example, the outside of the dura mater of the animal, and the external pressure is applied to the brain tissue of the animal. The method for applying the external pressure is, for example, the arterial patch method used in the above-mentioned effect experiment, and the external pressure may be applied using the device for regulating molecular transport in the extracellular space of the brain shown in FIG. 1.

[0054] As can be seen from the above effect experiments, the physical method for regulating molecular transport in the extracellular space of the brain can effectively regulate molecular transport in the extracellular space of the brain.

[0055] The series of detailed descriptions recited above are merely specific descriptions of possible embodiments of the present invention, and do not limit the protection scope of the present invention. Any equivalent embodiments or modifications made without departing from the technical idea of ​​the present invention, such as combinations, divisions, or overlaps of features, should be included in the protection scope of the present invention. [Explanation of symbols]

[0056] 10 Detection mechanism 30 Pressurizing mechanism 31 Flexible Bag 32 Fluid container 33 Fluid filling and discharging unit 331 Intake pipe 332 Gas Compressor 333 Exhaust Pipe 334 Exhaust valve 335 Flow meter 336 Intake valve 50 Control Mechanism 51 Preamp 52 High Pass Filter 53 Pulse amplitude and frequency extraction circuit 54 Microcontrollers 60 display units 70 Pressure Sensor 80 Input mechanism 91 Skull 92 Dura mater 93 Pia mater

Claims

1. A physical method for regulating molecular transport in the extracellular space of the brain, comprising applying external pressure to brain tissue of an animal, the rhythm of the application of the external pressure being associated with the automaticity of the animal.

2. 2. The physical method of regulating molecular transport in the extracellular space of the brain according to claim 1, wherein said automaticity is respiratory rhythm, cardiac rhythm, cerebral pulsation rhythm or vascular pulsation rhythm.

3. 2. The physical method of modulating molecular transport in the extracellular space of the brain of claim 1, comprising applying external pressure to the brain tissue of the animal outside the dura mater of the animal.

4. A detection mechanism (10) capable of detecting the motility of an animal; a pressure mechanism (30) capable of applying external pressure to the animal's brain tissue; a control mechanism (50) capable of controlling the pressure mechanism (30) so that the rhythm of applying external pressure by the pressure mechanism (30) is associated with the motility of the animal based on the detection result of the detection mechanism (10); A device for regulating molecular transport in the extracellular space of the brain, comprising:

5. The device for regulating molecular transport in the extracellular space of the brain according to claim 4 , wherein the automaticity is respiratory rhythm, cardiac rhythm, cerebral pulsation rhythm or vascular pulsation rhythm.

6. The pressure mechanism (30) A flexible bag (31) that is filled with a fluid and thereby capable of applying external pressure to the animal's brain tissue; A fluid container (32) for storing a fluid; a fluid filling and discharging unit (33) connected to the flexible bag (31) and the fluid container (32); Including, 5. The device for regulating molecular transport in the extracellular space of the brain as described in claim 4, wherein the fluid filling and discharging unit (33) is capable of filling the flexible bag (31) with fluid stored in the fluid container (32), the fluid filling and discharging unit (33) is also capable of discharging the fluid in the flexible bag (31), and the control mechanism (50) is capable of controlling the fluid filling and discharging unit (33).

7. The device for regulating molecular transport in the extracellular space of the brain as described in claim 6, wherein the detection mechanism (10) is an electrocardiograph, the control mechanism (50) is capable of extracting QRS waves and T waves from the detection results of the detection mechanism (10), and the control mechanism (50) is capable of controlling the fluid filling and discharging unit (33) to fill the flexible bag (31) with fluid at the start of the QRS wave and to discharge fluid from the flexible bag (31) at the end of the T wave.

8. The fluid filling and discharging unit (33) comprises: an intake pipe (331) having one end connected to the flexible bag (31); a gas compressor (332) having an outlet connected to the other end of the intake pipe (331) and an inlet connected to the fluid container (32); an exhaust pipe (333) having one end connected to the flexible bag (31); an exhaust valve (334) connected to the other end of the exhaust pipe (333); Including, 7. The device for regulating molecular transport in the extracellular space of the brain as described in claim 6, wherein the control mechanism (50) is capable of controlling the gas compressor (332) and the exhaust valve (334).

9. the fluid filling and discharging unit (33) further includes a flow meter (335), the flow meter (335) is provided in the intake pipe (331) and the exhaust pipe (333) and detects the volume of fluid flowing through the intake pipe (331) and the exhaust pipe (333), the flow meter (335) is connected to the control mechanism (50), and the control mechanism (50) is capable of integrating a total intake volume and / or a total exhaust volume based on the detection result of the flow meter (335); The device for regulating molecular transport in the extracellular space of the brain as described in claim 8, further comprising a display unit (60) connected to the control mechanism (50), the control mechanism (50) being capable of controlling the display unit (60) to display the detection result of the detection mechanism (10), the total inhalation volume and / or the total exhalation volume.

10. The pressure mechanism (30) a motor whose operation is controllable by said control mechanism (50); A presser plate connected to an output end of the motor; Including, The device for regulating molecular transport in the extracellular space of the brain according to claim 4 , wherein the motor is capable of driving the pressure plate so as to move and apply external pressure to animal brain tissue.

11. 5. The device for regulating molecular transport in the extracellular space of the brain as described in claim 4, further comprising a pressure sensor (70) provided in the pressure mechanism (30) and detecting the pressure applied from the pressure mechanism (30) to the brain tissue, the pressure sensor (70) being connected to the control mechanism (50), and the control mechanism (50) being capable of controlling the pressure mechanism (30) based on the detection result of the pressure sensor (70) so that the maximum value of the external pressure applied from the pressure mechanism (30) to the animal's brain tissue satisfies a set value.

12. 12. The device for regulating molecular transport in the extracellular space of the brain as described in claim 11, further comprising an input mechanism (80) connected to the control mechanism (50), the input mechanism (80) enabling operating parameters and on-off signals to be input to the control mechanism (50), the operating parameters including a maximum setting value for the external pressure applied to the animal's brain tissue from the pressure mechanism (30).

Images