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 of an animal, comprising applying external pressure to the brain tissue of the animal, the rhythm of the application of the external pressure being correlated with the animal's spontaneous rhythmicity. An apparatus for regulating molecular transport in the extracellular space of the brain of an animal, comprising a detecting mechanism (10), a pressurizing mechanism (30), and a control mechanism (50). The detecting mechanism (10) is capable of detecting the spontaneous rhythmicity of the animal. The pressurizing mechanism (30) is capable of applying external pressure to the brain tissue of the animal. The control mechanism (50) is capable of controlling the pressurizing mechanism (30) in accordance with the detection result of the detecting mechanism (10), so that the rhythm of the application of the external pressure by the pressurizing mechanism (30) is correlated with the spontaneous rhythmicity of the animal. The method and apparatus can effectively regulate molecular transport in the extracellular space of the brain.

Description

Physical method and device for regulating molecular transport in brain extracellular space Technical Field

[0001] The patent of this invention relates to a physical method and device for regulating the transport of molecules in the extracellular space of brain cells. Background Art

[0002] The extracellular space (ECS) is a tortuous space between brain cells and between cells and blood vessels. Substances in this space are transported by both convection and diffusion. New drug delivery methods via the ECS successfully bypass the blood-brain barrier, which hinders most drugs from entering the brain. This offers new hope for drugs that have previously failed to reach the brain through oral and intravenous routes.

[0003] The factors influencing substance transport within the ECS are complex. Neural excitation and the release of transmitters following excitation can both alter the rate of substance transport within the ECS (Y. Li et al., 2020; Shi et al., 2015). Multiple factors, including sleep (Xie et al., 2013), anesthesia (Zhao et al., 2020), neural excitation (Shi et al., 2015), and development (R. Wang et al., 2021), can positively or negatively regulate the drainage of interstitial fluid (ISF) within the ECS. These factors provide important theoretical foundations and technical approaches for exploring ECS-based stroke treatments. For example, pain stimulation (Shi et al., 2015) and olfactory stimulation can slow down ISF drainage; light can promote the excretion of ab out of the brain by accelerating ISF drainage, thereby treating Alzheimer's disease (AD) (Yue et al., 2019); different days of simulated weightlessness (Gao et al., 2021) and different types of anesthesia (Zhao et al., 2020) can positively or negatively regulate ISF drainage.

[0004] Currently, more effective methods are needed to regulate the transport of molecules within the extracellular space of the brain.

[0005] Summary of the Invention

[0006] The purpose of the present invention is to provide a new method for effectively regulating the transport of molecules in the extracellular space of brain cells.

[0007] Another object of the present invention is to provide a device that can effectively regulate the transport of molecules in the extracellular space of the brain.

[0008] The present invention provides a physical method for regulating molecular transport in the extracellular space of the brain, comprising applying external pressure to the brain tissue of an animal, wherein the rhythm of applying the external pressure is related to the automatic rhythmicity of the animal.

[0009] The physical method for regulating the transport of molecules in the extracellular space of the brain can effectively regulate the transport of molecules in the extracellular space of the brain.

[0010] In another exemplary embodiment of the physical method for regulating molecular transport in the extracellular space of the brain, the automatic rhythmicity is the respiratory rhythm, the heart rhythm, the brain pulsation rhythm or the blood vessel pulsation rhythm.

[0011] In yet another illustrative embodiment of a physical method for modulating molecular transport within the extracellular space of the brain, external pressure is applied to brain tissue of the animal outside of the dura mater of the animal.

[0012] The present invention also provides a device for regulating molecular transport within the extracellular space of the brain, comprising: a detection mechanism, a pressure mechanism, and a control mechanism. The detection mechanism is capable of detecting the autorhythmicity of an animal. The pressure mechanism is capable of applying external pressure to the animal's brain tissue. The control mechanism is capable of controlling the pressure mechanism based on the detection results of the detection mechanism, such that the rhythm of the external pressure applied by the pressure mechanism is correlated with the autorhythmicity of the animal. This device for regulating molecular transport within the extracellular space of the brain can effectively regulate molecular transport within the extracellular space of the brain through physical methods.

[0013] In another exemplary embodiment of the device for regulating molecular transport in the brain extracellular space, the automatic rhythmicity is a respiratory rhythm, a cardiac rhythm, a brain pulsation rhythm, or a blood vessel pulsation rhythm.

[0014] In another exemplary embodiment of a device for regulating molecular transport within the extracellular space of brain cells, a pressurizing mechanism includes a flexible bladder, a fluid container, and a fluid charging and discharging unit. The flexible bladder is capable of applying external pressure to an animal's brain tissue by being filled with fluid. The fluid container is used to store the fluid. The fluid charging and discharging unit connects the flexible bladder and the fluid container and is capable of filling the flexible bladder with fluid stored in the fluid container and discharging the fluid from the flexible bladder. A control mechanism is capable of controlling the fluid charging and discharging unit.

[0015] In another exemplary embodiment of the device for regulating molecular transport in the extracellular space of brain cells, the detection mechanism is an electrocardiogram monitor, and the control mechanism can extract the QRS wave and T wave from the detection results of the detection mechanism; the control mechanism can control the fluid charging and discharging unit to fill the flexible bag with fluid at the starting point of the QRS wave, and can control the fluid charging and discharging unit to discharge fluid from the flexible bag at the end point of the T wave.

[0016] In another illustrative embodiment of a device for regulating molecular transport within the extracellular space of the brain, a fluid charging and discharging unit includes an inlet pipe, a gas compressor, an exhaust pipe, and an exhaust valve. One end of the inlet pipe is connected to a flexible bladder, and the other end is connected to the outlet of the gas compressor. The inlet of the gas compressor is connected to a fluid container. One end of the exhaust pipe is connected to the flexible bladder, and the other end is connected to the exhaust valve. A control mechanism is capable of controlling the gas compressor and the exhaust valve.

[0017] In another exemplary embodiment of the device for regulating molecular transport in the extracellular space of brain cells, the fluid charging and discharging unit further includes an air inlet valve disposed between the gas compressor and the fluid container.

[0018] In another exemplary embodiment of the device for regulating molecular transport within the extracellular space of the brain, the fluid charging and discharging unit further includes a flowmeter connected to a control mechanism. The flowmeter is disposed in the intake and exhaust pipes to detect the volume of fluid flowing through the intake and exhaust pipes. The control mechanism is capable of integrating the total intake and / or exhaust volume based on the detection results of the flowmeter. The device further includes a display unit connected to the control mechanism, which is capable of controlling the display unit to display the detection results of the detection mechanism, the total intake and / or exhaust volume.

[0019] In another exemplary embodiment of a device for regulating molecular transport in the extracellular space of brain cells, a pressure mechanism includes a motor and a pressure plate. A control mechanism is capable of controlling the operation of the motor. The pressure plate is connected to an output terminal of the motor, and the motor is capable of driving the pressure plate to apply external pressure to the brain tissue of an animal.

[0020] In another exemplary embodiment of the device for regulating molecular transport in the extracellular space of the brain, the device further comprises a pressure sensor. The pressure sensor is disposed on the pressurizing mechanism and is configured to detect the pressure applied by the pressurizing mechanism to the brain tissue. The pressure sensor is connected to a control mechanism, which is configured to control the pressurizing mechanism based on the detection result of the pressure sensor so that the maximum external pressure applied by the pressurizing mechanism to the animal's brain tissue meets a set value.

[0021] In another exemplary embodiment of the device for regulating molecular transport in the brain extracellular space, the device further comprises an input mechanism. The input mechanism is connected to the control mechanism, and operating parameters and power-on / off signals can be input to the control mechanism via the input mechanism. The operating parameters include a set value for the maximum external pressure applied by the pressurizing mechanism to the animal's brain tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The following drawings are only used to schematically illustrate and explain the present invention and are not intended to limit the scope of the present invention.

[0023] FIG1 and FIG2 are schematic structural diagrams illustrating an exemplary embodiment of a device for regulating molecular transport in the extracellular space of the brain.

[0024] FIG3 is a schematic structural diagram of a pressurizing mechanism of the device for regulating molecular transport in the extracellular space of brain cells shown in FIG1 .

[0025] 4A to 4D are MRI scan images from the effect experiment.

[0026] Figures 5 to 8 are histograms of the structural characteristic values ​​of the brain ECS in the effect experiment.

[0027] 9A to 9D are two-dimensional graphs reflecting the diffusion coefficients of molecules within the brain ECS.

[0028] 10A to 10D are three-dimensional graphs reflecting molecular diffusion coefficients within the brain ECS.

[0029] Description of labels

[0030] 10 Detection mechanism

[0031] 30 Pressurizing mechanism

[0032] 31 Flexible capsule

[0033] 32 fluid container

[0034] 33 Fluid charging and discharging unit

[0035] 331 Intake pipe

[0036] 332 Gas Compressor

[0037] 333 exhaust pipe

[0038] 334 exhaust valve

[0039] 335 flow meter

[0040] 336 Intake valve

[0041] 50 Control mechanism

[0042] 51 Preamplifier

[0043] 52 High-pass filter

[0044] 53 Pulse amplitude and frequency extraction circuit

[0045] 54 microcontroller

[0046] 60 display units

[0047] 70 Pressure Sensor

[0048] 80 Input mechanism

[0049] 91 Skull

[0050] 92 dura mater

[0051] 93 pia mater DETAILED DESCRIPTION

[0052] In order to have a clearer understanding of the technical features, purposes and effects of the invention, the specific embodiments of the present invention are now described with reference to the accompanying drawings. The same reference numerals in the drawings represent components with the same structure or similar structures but the same functions.

[0053] In this document, “illustrative” means “serving as an example, instance or illustration”, and any diagram or implementation described in this document as “illustrative” should not be interpreted as a more preferred or more advantageous technical solution.

[0054] To simplify the drawings, each figure schematically shows only the parts related to the present invention, which do not represent the actual structure of the product.

[0055] Figure 1 is a schematic diagram illustrating an exemplary embodiment of a device for regulating molecular transport in the extracellular space of the brain. As shown in Figure 1 , the device for regulating molecular transport in the extracellular space of the brain includes a detection mechanism 10, a pressurizing mechanism 30, and a control mechanism 50.

[0056] The detection mechanism 10 is capable of detecting the animal's automatic rhythmicity. Generally speaking, automaticity refers to a system that continues to function without external stimulation. In physiology, automaticity generally refers to a part of the body or an organ that continues to function without further stimulation. Examples of an animal's automatic rhythmicity include respiratory rhythm, heart rhythm, brain pulsation rhythm, or vascular pulsation rhythm. When the automatic rhythmicity is heart rhythm, the detection mechanism 10 is, for example, an electrocardiogram (ECG) monitor.

[0057] The pressurizing mechanism 30 is capable of applying external pressure to the animal's brain tissue. This external pressure refers to the force exerted on the brain tissue by structures other than the brain tissue. Figure 3 is a schematic diagram of the specific structure of the pressurizing mechanism. Specifically, as shown in Figure 3, in this exemplary embodiment, the pressurizing mechanism 30 includes a flexible bladder 31, a fluid container 32 for storing fluid, and a fluid charging and discharging unit 33. The flexible bladder 31 is capable of applying external pressure to the animal's brain tissue by being filled with fluid. As shown in Figures 1 and 2, during use, the flexible bladder 31 is placed, for example, between the animal's skull 91 and the dura mater 92. However, this is not limiting. In other use cases, the flexible bladder 31 can also be placed on the side of the animal's dura mater 92 facing away from the skull 91. The flexible bladder 31 is made, for example, of a high-molecular-weight polyurethane material, exhibiting excellent flexibility. It is sized to fit between the skull 91 and the dura mater 92 and is as thin as possible. Figure 1 shows the flexible bladder 31 after the fluid is discharged, while Figure 2 shows the flexible bladder 31 filled with fluid and applying pressure to the brain tissue. The fluid is, for example, a gas, such as helium. In other exemplary embodiments, the fluid may also be a liquid. A fluid charging and discharging unit 33 connects the flexible bladder 31 and the fluid container 32. The fluid charging and discharging unit 33 can charge the fluid stored in the fluid container 32 into the flexible bladder 31. The fluid charging and discharging unit 33 can also discharge the fluid from the flexible bladder 31. In the exemplary embodiment, the fluid container 32 is, for example, a high-pressure gas tank.

[0058] Specifically, as shown in FIG3 , in this exemplary embodiment, the fluid charging and discharging unit 33 includes, for example, an air inlet pipe 331, a gas compressor 332, an exhaust pipe 333, and an exhaust valve 334. One end of the air inlet pipe 331 is connected to the flexible bladder 31. The outlet of the gas compressor 332 is connected to the other end of the air inlet pipe 331, and the inlet is connected to the fluid container 32. One end of the exhaust pipe 333 is connected to the flexible bladder 31. The exhaust valve 334, for example, a solenoid valve, is connected to the other end of the exhaust pipe 333.

[0059] The control mechanism 50 can control the pressurizing mechanism 30 based on the detection results of the detection mechanism 10, so that the rhythm of the external pressure applied by the pressurizing mechanism 30 is related to the animal's automatic rhythmicity. 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.

[0060] The device for regulating molecular transport in the extracellular space of brain cells can apply external pressure to the brain tissue of an animal, and the rhythm of applying the external pressure is related to the automatic rhythmicity of the animal.

[0061] In the exemplary embodiment, the fluid charging and discharging unit 33 further includes an air inlet valve 336 disposed between the gas compressor 332 and the fluid container 32 .

[0062] In this exemplary embodiment, the detection mechanism 10 is, for example, an electrocardiogram (ECG) monitor, and the control mechanism 50 is, for example, capable of extracting the QRS wave and the T wave from the detection results of the detection mechanism 10. The control mechanism 50 is capable of controlling the fluid charging and discharging unit 33 to fill the flexible capsule 31 with fluid at the starting point of the QRS wave, and is capable of controlling the fluid charging and discharging unit 33 to discharge fluid from the flexible capsule 31 at the end point of the T wave. This facilitates precise 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 ECG signal measured by the ECG monitor passes through the preamplifier 51 and the high-pass filter 52 to remove the baseline, and then enters the pulse amplitude and frequency extraction circuit 53, where it is shaped into a digital pulse and then sent to the microcontroller 54. The microcontroller 54 is capable of controlling the exhaust valve 334 and the intake valve 336.

[0063] As shown in FIG3 , in the exemplary embodiment, the fluid charging and discharging unit 33 further includes a flow meter 335 . The flow meter 335 is disposed on 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 accumulate the total intake and / or exhaust volume based on the detection results of the flow meter 335 , thereby facilitating user monitoring of the device's operation.

[0064] As shown in FIG1 , in an exemplary embodiment, the device for regulating molecular transport in the brain extracellular space further includes a display unit 60 connected to a control mechanism 50. The control mechanism 50 can control the display unit 60 to display the detection results of the detection mechanism 10, the total intake volume and / or the total exhaust volume, etc., so that the user can monitor the operation of the device.

[0065] As shown in FIG1 , in an exemplary embodiment, the device for regulating molecular transport within the brain extracellular space further includes a pressure sensor 70, which is disposed on the pressurizing mechanism 30 and is used to detect the pressure applied by the pressurizing mechanism 30 to the brain tissue. Pressure sensor 70 is connected to a control mechanism 50. The control mechanism 50 can control the pressurizing mechanism 30 based on the detection results of the pressure sensor 70, so that the maximum external pressure applied by the pressurizing mechanism 30 to the animal's brain tissue meets a set value. This facilitates control over the magnitude of the applied pressure.

[0066] As shown in FIG1 , in an exemplary embodiment, the device for regulating molecular transport within the extracellular space of the brain further includes an input mechanism 80 connected to the control mechanism 50. Operating parameters and power-on / off signals can be input to the control mechanism 50 via the input mechanism 80. The operating parameters include a set value for the maximum external pressure applied by the pressurizing mechanism 30 to the animal's brain tissue. The input mechanism 80 is, for example, a key. However, the present invention is not limited thereto. In other exemplary embodiments, the input mechanism 80 can also be, for example, a knob or a touch mechanism (e.g., a touch keyboard). This facilitates user control of the device.

[0067] In an exemplary embodiment, the device for regulating molecular transport in the extracellular space of the brain further comprises a battery to provide electrical energy required for operation.

[0068] In other exemplary embodiments, the pressurizing mechanism may further include, for example, a motor and a pressure plate. A control mechanism may control the operation of the motor. The pressure plate is connected to the output terminal of the motor, and the motor may drive the pressure plate to apply external pressure to the animal's brain tissue. However, this is not limiting, and the pressurizing mechanism may also be other structures capable of applying external pressure to the animal's brain tissue.

[0069] The following experiments verify the effect of applying external pressure to the brain tissue of an animal, where the rhythm of the external pressure is related to the animal's automatic rhythmicity, on the transport of molecules in the extracellular space of the brain.

[0070] Effect experiment

[0071] In this experiment, external pressure was applied to the rat's brain tissue using the pulsation of the rat's own artery, so that the rhythm of the applied external pressure was the same as the rhythm of the arterial vascular pulsation.

[0072] The rats were randomly divided into four groups according to the experimental requirements:

[0073] Control group (Group A): no arterial patching was performed;

[0074] Arterial patch surgery group (Group B): Arterial patching and ipsilateral contrast agent were performed;

[0075] Arterial patch surgery contralateral group (Group C): Arterial patching and contralateral contrast agent were performed;

[0076] Arterial patching followed by gelatin sponge padding group (Group D): Arterial patching, ipsilateral contrast agent and gelatin sponge patching were performed.

[0077] 1. Experimental Animal Handling

[0078] Arterial patching: The rat's own artery was patched onto the right epidural mater.

[0079] Ipsilateral contrast agent: Contrast agent was present in the right caudate nucleus of the rat.

[0080] Contralateral contrast agent: Contrast agent was present in the left caudate nucleus of the rat.

[0081] Gelatin sponge patch: Gelatin sponge is placed under the artery for arterial patching to resist the effect of arterial pulsation.

[0082] 2. MRI scanning and data post-processing

[0083] Rats were placed in the prone position for MRI scanning, and images were acquired until the contrast agent had completely diffused. The acquired images are shown in Figures 4A, 4B, 4C, and 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; 15-240 min: time point of image acquisition.

[0084] NanoDetect analysis software was used to post-process the MRI scan results to obtain the following parameters: contrast agent elimination half-life (T1 / 2), molecular diffusion coefficient within the brain ECS (D*), brain ECS tortuosity (λ), and brain ECS volume fraction (α). The results are shown in Figures 5, 6, 7, and 8, respectively.

[0085] 3. Results Analysis

[0086] As shown in Figures 4A to 4D, the contrast agent diffused from the caudate nucleus to the ipsilateral superficial cortex. The bright white contrast agent spots in Figures 4A to 4D disappeared at roughly the same rate, which is believed to be due to the insufficient resolution of the MRI images.

[0087] As shown in Figures 5 to 8, the arterial patch surgery group (Group B) had a shorter contrast agent clearance half-life (T1 / 2), a higher molecular diffusion coefficient within the brain ECS (D*), a smaller brain ECS tortuosity (λ), and a higher brain ECS volume fraction (α) at ​​1, 3, 7, and 15 days compared to the other groups. This suggests that arterial patching can accelerate ISF drainage within rat brain tissue, enhance microscopic molecular diffusion, reduce tortuosity, and expand the brain ECS space. However, no statistical differences were observed in the aforementioned parameters between the contralateral arterial patch surgery group (Group C) and the gelatin sponge gasket group after arterial patching (Group D) and the control group (Group A).

[0088] The conclusion that arterial patching can enhance the molecular diffusion coefficient within the brain ECS is also clearly demonstrated in the D-mapping visualization of the molecular diffusion coefficient within the brain ECS. Figures 9A, 9B, 9C, and 9D are two-dimensional plots of the molecular diffusion coefficient within the brain ECS, corresponding to Groups A, B, C, and D, respectively. Figures 10A, 10B, 10C, and 10D are three-dimensional plots of the molecular diffusion coefficient within 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 reflect the magnitude of the molecular diffusion coefficient within the brain ECS. As shown in the figures, the arterial patching group (Group B) had the highest molecular diffusion coefficient within the brain ECS compared to the other three groups, indicating the fastest molecular diffusion capacity within the brain ECS.

[0089] 4. Experimental Conclusion

[0090] The experimental results above show that compared with the control group (Group A), rats in the arterial patch surgery group (Group B) experienced accelerated brain ISF drainage. This change was detectable from the first day after surgery and persisted until 15 days. No significant difference was observed in the contralateral group (Group C), indicating that arterial patch surgery can effectively and long-term improve ISF drainage from the ipsilateral deep to superficial brain layers, while no significant improvement was observed in contralateral brain ISF drainage. This suggests that it has a regional regulatory effect.

[0091] According to the above experimental results, there was no significant difference in brain ISF drainage between the gelatin sponge spacer group (Group D) and the control group (Group A) after arterial patching. This indicates that brain ISF drainage returned to normal after blocking the arterial pulsation effect. The results in Figures 5 to 10 demonstrate that arterial patching can accelerate brain ISF drainage, accompanied by an increase in the brain ECS space, a decrease in tortuosity, and an enhancement of molecular diffusion capacity.

[0092] This suggests that epidural arterial patching can promote molecular diffusion within the brain ECS, accompanied by structural changes in the brain ECS.

[0093] The above-mentioned effect experiment used the rat's own artery to apply external pressure to the rat's brain tissue. It is understandable that the device for regulating molecular transport in the brain extracellular space shown in Figure 1 can also be used to replace the artery 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 to achieve the same effect as the arterial patch surgery group (Group B) in the above-mentioned effect experiment, namely, accelerating the brain ISF drainage rate, increasing the brain ECS space share, reducing tortuosity, and enhancing molecular diffusion capacity. This device for regulating molecular transport in the brain extracellular space can effectively regulate molecular transport in the brain extracellular space.

[0094] The present invention also provides a physical method for regulating the transport of molecules in the extracellular space of the brain, which includes applying external pressure to the brain tissue of an animal, and the rhythm of applying the external pressure is related to the automatic rhythmicity of the animal. Among them, the automatic rhythmicity is, for example, the respiratory rhythm, heart rhythm, brain pulsation rhythm or blood vessel pulsation rhythm. The location where the external pressure is applied is, for example, applying external pressure to the brain tissue of the animal outside the dura mater of the animal. The way of applying external pressure is, for example, the arterial patch method adopted in the above-mentioned effect experiment, or the device for regulating the transport of molecules in the extracellular space of the brain as shown in Figure 1 can be used to apply external pressure.

[0095] According to the above effect experiments, it can be seen that the physical method of regulating the transport of molecules in the extracellular space of the brain can effectively regulate the transport of molecules in the extracellular space of the brain.

[0096] The series of detailed descriptions listed above are only specific descriptions of feasible embodiments of the present invention. They are not intended to limit the scope of protection of the present invention. Any equivalent implementation scheme or changes that do not deviate from the technical spirit of the present invention, such as the combination, division or repetition of features, should be included in the scope of protection of the present invention.

Claims

1. A physical method for regulating molecular transport in the extracellular space of the brain, characterized in that: It involves applying external pressure to the brain tissue of an animal, the rhythm of which is correlated with the animal's automatic rhythmicity.

2. The physical method for regulating molecular transport in the extracellular space of brain according to claim 1, wherein: The automatic rhythmicity is respiratory rhythm, heart rhythm, brain pulsation rhythm or blood vessel pulsation rhythm.

3. The physical method for regulating molecular transport in the extracellular space of brain according to claim 1, wherein: External pressure is applied to the animal's brain tissue outside of the animal's dura mater.

4. A device for regulating molecular transport in the extracellular space of the brain, characterized in that include: a detection mechanism (10) capable of detecting the animal's automatic rhythmicity; a compression mechanism (30) capable of applying external pressure to brain tissue of the animal; as well as A control mechanism (50) is capable of controlling the pressurizing mechanism (30) according to the detection result of the detection mechanism (10) so that the rhythm of the external pressure applied by the pressurizing mechanism (30) is related to the automatic rhythmicity of the animal.

5. The device for regulating molecular transport in the extracellular space of brain according to claim 4, wherein: The automatic rhythmicity is respiratory rhythm, heart rhythm, brain pulsation rhythm or blood vessel pulsation rhythm.

6. The device for regulating molecular transport in the extracellular space of brain according to claim 4, wherein: The pressurizing mechanism (30) comprises: a flexible bladder (31) capable of applying external pressure to the brain tissue of an animal by filling it with a fluid, a fluid container (32) for storing fluid, and A fluid charging and discharging unit (33) is connected to the flexible sac (31) and the fluid container (32). The fluid charging and discharging unit (33) can charge the fluid stored in the fluid container (32) into the flexible sac (31). The fluid charging and discharging unit (33) can also discharge the fluid in the flexible sac (31). The control mechanism (50) can control the fluid charging and discharging unit (33).

7. The device for regulating molecular transport in the extracellular space of brain according to claim 6, wherein: The detection mechanism (10) is an electrocardiogram monitor, and the control mechanism (50) can extract the QRS wave and the T wave from the detection result of the detection mechanism (10); the control mechanism (50) can control the fluid charging and discharging unit (33) to fill the flexible bag (31) with fluid at the starting point of the QRS wave, and can control the fluid charging and discharging unit (33) to discharge the fluid from the flexible bag (31) at the end point of the T wave.

8. The device for regulating molecular transport in the extracellular space of brain according to claim 6, wherein: The fluid charging and discharging unit (33) comprises: an air inlet pipe (331), one end of which is connected to the flexible bag (31), A gas compressor (332), whose outlet is connected to the other end of the air inlet pipe (331) and whose inlet is connected to the fluid container (32), an exhaust pipe (333), one end of which is connected to the flexible bag (31), and An exhaust valve (334) is connected to the other end of the exhaust pipe (333), and the control mechanism (50) is capable of controlling the gas compressor (332) and the exhaust valve (334).

9. The device for regulating molecular transport in the extracellular space of brain according to claim 8, wherein: The fluid charging and discharging unit (33) further includes a flow meter (335), which is provided at the intake pipe (331) and the exhaust pipe (333) to detect the volume of the 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 accumulating the total intake volume and / or the total exhaust volume according to the detection result of the flow meter (335); The device further comprises a display unit (60), wherein the display unit (60) is connected to the control mechanism (50), and the control mechanism (50) is capable of controlling the display unit (60) to display the detection result of the detection mechanism (10), the total intake volume and / or the total exhaust volume.

10. The device for regulating molecular transport in the extracellular space of brain according to claim 4, wherein: The pressurizing mechanism (30) comprises: an electric motor, the control mechanism (50) is capable of controlling the movement of the electric motor, and A pressing plate is connected to the output end of the motor, and the motor is capable of driving the pressing plate to move so as to apply external pressure to the brain tissue of the animal.

11. The device for regulating molecular transport in the extracellular space of brain according to claim 4, wherein: The device further includes a pressure sensor (70), which is arranged on the pressurizing mechanism (30) and is used to detect the pressure applied by the pressurizing mechanism (30) to the brain tissue. The pressure sensor (70) is connected to the control mechanism (50), and the control mechanism (50) can control the pressurizing mechanism (30) according to the detection result of the pressure sensor (70) so that the maximum value of the external pressure applied by the pressurizing mechanism (30) to the brain tissue of the animal meets a set value.

12. The device for regulating molecular transport in the extracellular space of brain according to claim 11, wherein: The device further comprises an input mechanism (80) connected to the control mechanism (50), and is capable of inputting operating parameters and on / off signals into the control mechanism (50) through the input mechanism (80), wherein the operating parameters include a set value of the maximum value of the external pressure applied by the pressurizing mechanism (30) to the brain tissue of the animal.

Images