Synchronous blood-brain microdialysis sampling device suitable for freely moving rats under exposure of aerosol

Abstract

The utility model discloses a blood-brain synchronous microdialysis sampling device suitable for a freely moving rat under aerosol exposure. The blood-brain synchronous microdialysis sampling device comprises an aerosol generator, an aerosol exposure cavity, a particulate matter concentration monitor, an injection pump, a brain microdialysis probe, a blood microdialysis probe, a double-channel cooling trace collector and an air extracting pump, the brain microdialysis probe is used for being implanted into the brain area of an animal, and the blood microdialysis probe is used for being implanted into the jugular vein of the animal; the injection pump comprises a first Ringer's solution output port and a second Ringer's solution output port; the dual-channel cooling trace collector comprises a first collecting opening and a second collecting opening; and the output ports of the sucking pump, the particulate matter concentration monitor and the aerosol generator are communicated with the hollow cavity. According to the blood-brain synchronous microdialysis sampling device suitable for the freely moving rats under the exposure of the aerosol, the animals are exposed in a nicotine aerosol environment when the animals are sober and freely moving, and the regulation effect on animal neurotransmitters after nicotine inhalation is reflected more truly.

Description

Technical Field

[0001] The utility model relates to the technical field of animal aerosol, and more specifically, to a blood-brain synchronous microdialysis sampling device suitable for freely moving rats under aerosol exposure. Background Art

[0002] Nicotine is an important characteristic component of tobacco, and nicotine dependence is the fundamental cause of tobacco dependence and repeated use of tobacco products. Nicotine dependence stems from nicotine activating nicotinic acetylcholine receptors in the central nervous system, enhancing the activity of dopaminergic neurons in the ventral tegmental area of the mesolimbic reward system, and causing a large amount of dopamine to be released at the terminals of dopaminergic neurons in the nucleus accumbens. In addition, other neurotransmitters, such as serotonin, γ-aminobutyric acid, acetylcholine, etc., are all involved in regulating the nerve activities caused by nicotine. Therefore, accurately evaluating the metabolism of nicotine in the body and the changes in neurotransmitters it causes is of great significance for understanding nicotine dependence.

[0003] Currently, for the study of nicotine metabolism and the changes in neurotransmitters it causes, animals are usually sacrificed by injecting nicotine intraperitoneally, subcutaneously, or intravenously, then the brain is taken and homogenized for further analysis. This method requires sacrificing a large number of experimental animals and cannot be used for real-time continuous evaluation of the changes in neurotransmitters caused by nicotine. In addition, after injecting nicotine intraperitoneally, subcutaneously, or intravenously, nicotine must undergo first-pass metabolism in the liver before entering the brain, which is quite different from the metabolic process of nicotine in the body after humans inhale tobacco products by suction.

[0004] Nicotine aerosol exposure can expose nicotine in a way closer to human inhalation of tobacco products. In addition, as a minimally invasive technique, microdialysis technology combines perfusion and dialysis by implanting a semipermeable membrane probe into the body, enabling in vivo continuous and dynamic sampling in the same animal, making it of important application value in neuroscience, pharmacokinetics, and pharmacodynamics. However, currently commercially available aerosol exposure devices need to completely bind experimental animals in a fixator, which can only be used for animals to inhale aerosol for a long time and cannot perform microdialysis sampling while inhaling aerosol. Moreover, binding animals in a fixator and preventing them from moving will affect the accurate evaluation of neurotransmitter changes. Therefore, designing a device that allows animals to inhale nicotine by aerosol exposure in a freely moving state while performing blood-brain synchronous microdialysis sampling is of great significance for studying the metabolism of nicotine in the body and the changes in neurotransmitters caused by human inhalation of tobacco products. Summary of the Utility Model

[0005] In view of this, the purpose of the present utility model is to provide a blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure, so that when the animal is awake and freely moving and exposed to a nicotine aerosol environment, it can more truly reflect the regulatory effect of nicotine inhalation on the neurotransmitters of the animal.

[0006] Based on the above purpose, the present utility model provides a blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure, which includes an aerosol generator, an aerosol exposure chamber, a particulate matter concentration monitor, an infusion pump, a brain microdialysis probe, a blood microdialysis probe, a dual-channel cooling microcollector, and an air extraction pump. Among them: a hollow cavity is provided inside the aerosol exposure chamber, and the hollow cavity is used to place the animal; the brain microdialysis probe is used to implant into the brain region of the animal, and the blood microdialysis probe is used to implant into the jugular vein of the animal; the infusion pump includes a first Ringer's solution output port and a second Ringer's solution output port, the first Ringer's solution output port is communicated with the input end of the brain microdialysis probe, and the second Ringer's solution output port is communicated with the input end of the blood microdialysis probe; the dual-channel cooling microcollector includes a first collection port and a second collection port, the first collection port is communicated with the output end of the brain microdialysis probe, and the second collection port is communicated with the output end of the blood microdialysis probe; the suction port of the air extraction pump, the particulate matter concentration monitor, and the output port of the aerosol generator are all communicated with the hollow cavity.

[0007] Optionally, it further includes a first hose and a second hose. A first probe interface and a first collector port are opened at the top of the aerosol exposure chamber. One end of the first hose is connected and installed at the first Ringer's solution output port, the first hose extends into the hollow cavity through the first probe interface, and the other end of the first hose is connected and installed at the input end of the brain microdialysis probe; one end of the second hose is connected and installed at the first collection port, the second hose extends into the hollow cavity through the first collector port, and the other end of the second hose is connected and installed at the output end of the brain microdialysis probe.

[0008] Optionally, it further includes a third hose and a fourth hose. A second probe interface and a second collector port are further opened at the top of the aerosol exposure chamber. One end of the third hose is connected and installed at the second Ringer's solution output port, the third hose extends into the hollow cavity through the second probe interface, and the other end of the third hose is connected and installed at the output end of the blood microdialysis probe; one end of the fourth hose is connected and installed at the second collection port, the fourth hose extends into the hollow cavity through the second collector port, and the other end of the fourth hose is connected and installed at the output end of the blood microdialysis probe.

[0009] Optionally, a particulate matter concentration monitoring port is further opened at the top of the aerosol exposure cavity, and the particulate matter concentration monitor is sealed and installed on the particulate matter concentration monitoring port to monitor the particulate matter concentration in the hollow cavity.

[0010] Optionally, the aerosol exposure cavity further includes a first side surface, and an air extraction port is opened on the first side surface. The air extraction pump is connected to the hollow cavity through the air extraction port.

[0011] Optionally, the aerosol exposure cavity further includes a second side surface disposed opposite to the first side surface, and an aerosol input port is opened on the second side surface. The aerosol in the aerosol generator enters the hollow cavity through the aerosol input port.

[0012] Optionally, both the first hose and the second hose are PE tubes.

[0013] Optionally, both the third hose and the fourth hose are PE tubes.

[0014] Optionally, the aerosol generator includes a micro air compressor.

[0015] Optionally, the material of the aerosol exposure cavity is an acrylic glass plate.

[0016] The blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure provided by the present utility model includes an aerosol generator, an aerosol exposure cavity, a particulate matter concentration monitor, an injection pump, a brain microdialysis probe, a blood microdialysis probe, a dual-channel cooling micro collector, and an air extraction pump. When in use, the brain microdialysis probe and the blood microdialysis probe are respectively implanted into the brain and jugular vein of an animal in advance. The injection pump, the brain microdialysis probe, the blood microdialysis probe, and the dual-channel cooling micro collector are connected. First, the injection pump is turned on. After balancing for a period of time, then the aerosol generator and the air extraction pump are turned on for a period of time to ensure the stability of the aerosol concentration in the aerosol exposure cavity. When the animal is awake and freely moving, it is exposed to the nicotine aerosol environment. The dual-channel cooling micro collector continuously collects the brain microdialysis samples and the blood microdialysis samples. By analyzing the blood dialysis samples and the brain microdialysis samples, the regulatory effect of nicotine inhalation on the neurotransmitters of the animal can be more truly reflected. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The following will describe in detail the preferred embodiments of the present utility model with the help of the drawings, which will be helpful to understand the purpose and advantages of the present utility model, wherein:

[0018] Figure 1 It is a schematic structural diagram of the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure according to an embodiment of the present utility model.

[0019] Description of the reference numerals in the drawings:

[0020] 1: aerosol generator; 2: aerosol exposure chamber; 3: particulate matter concentration monitor; 4: syringe pump; 5: brain microdialysis probe; 6: blood microdialysis probe; 7: dual-channel cooling microcollector; 8: air extraction pump; 9: first Ringer's solution outlet; 10: second Ringer's solution outlet; 11: first collection port; 12: second collection port; 13: first hose; 14: second hose; 15: third hose; 16: fourth hose; 17: micro air compressor. Detailed implementation mode

[0021] The present utility model will be described in detail below in conjunction with the embodiments. The same components are denoted by the same reference numerals. It should be noted that the terms "front", "rear", "left", "right", "upper" and "lower" used in the following description refer to the directions in the drawings, and the terms "inner" and "outer" refer to the directions towards or away from the geometric center of a specific component respectively.

[0022] As Figure 1 shown, the blood-brain synchronous microdialysis sampling device applicable to freely moving rats under aerosol exposure provided by the present utility model includes an aerosol generator 1, an aerosol exposure chamber 2, a particulate matter concentration monitor 3, a syringe pump 4, a brain microdialysis probe 5, a blood microdialysis probe 6, a dual-channel cooling microcollector 7, and an air extraction pump 8, wherein: a hollow cavity is provided in the aerosol exposure chamber 2, and the hollow cavity is used to place an animal; the brain microdialysis probe 5 is used to implant into the brain region of the animal, and the blood microdialysis probe 6 is used to implant into the jugular vein of the animal; the syringe pump 4 includes a first Ringer's solution outlet 9 and a second Ringer's solution outlet 10, the first Ringer's solution outlet 9 is communicated with the input end of the brain microdialysis probe 5, and the second Ringer's solution outlet 10 is communicated with the input end of the blood microdialysis probe 6; the dual-channel cooling microcollector 7 includes a first collection port 11 and a second collection port 12, the first collection port 11 is communicated with the output end of the brain microdialysis probe 5, and the second collection port 12 is communicated with the output end of the blood microdialysis probe 6; the suction port of the air extraction pump 8, the particulate matter concentration monitor 3, and the output port of the aerosol generator 1 are all communicated with the hollow cavity.

[0023] It should be noted that: the model of the syringe pump 4 can be 8309020, 1 ml; the model of the dual-channel cooling microcollector 7 can be: MAB 85; the model of the aerosol generator 1 can be NSF-6A; the model of the particulate matter concentration monitor 3 can be HRH-AMC01; the model of the air extraction pump 8 can be R51029; the model of the brain microdialysis probe 5 can be CMA12; the model of the blood microdialysis probe 6 can be CMA20.

[0024] The present utility model provides a blood-brain synchronous microdialysis sampling device applicable to freely moving rats under aerosol exposure, which includes an aerosol generator 1, an aerosol exposure chamber 2, a particulate matter concentration monitor 3, an infusion pump 4, a brain microdialysis probe 5, a blood microdialysis probe 6, a dual-channel cooling microcollector 7, and an air extraction pump 8. When in use, the brain microdialysis probe 5 and the blood microdialysis probe 6 are respectively implanted into the brain and jugular vein of an animal in advance. The infusion pump 4, the brain microdialysis probe 5, the blood microdialysis probe 6, and the dual-channel cooling microcollector 7 are connected. First, the infusion pump 4 is turned on. After balancing for a period of time, the aerosol generator 1 and the air extraction pump 8 are then turned on for a period of time to ensure the stability of the aerosol concentration in the aerosol exposure chamber 2. When the animal is awake and freely moving, it is exposed to a nicotine aerosol environment, and the dual-channel cooling microcollector 7 continuously collects brain microdialysis samples and blood microdialysis samples. By analyzing the blood dialysis samples and brain microdialysis samples, the regulatory effect of nicotine inhalation on animal neurotransmitters can be more truly reflected.

[0025] As Figure 1 shown, it further includes a first hose 13 and a second hose 14. The top of the aerosol exposure chamber 2 is provided with a first probe interface and a first collector port. One end of the first hose 13 is connected and installed at the first Ringer's solution output port 9. The first hose 13 extends into the hollow cavity through the first probe interface. The other end of the first hose 13 is connected and installed at the input end of the brain microdialysis probe 5. One end of the second hose 14 is connected and installed at the first collection port 11. The second hose 14 extends into the hollow cavity through the first collector port. The other end of the second hose 14 is connected and installed at the output end of the brain microdialysis probe 5. In this embodiment, the specifications of the first hose 13 and the second hose 14 are 6.35×10.16 mm (inner diameter × outer diameter). The first Ringer's solution output port 9 is connected to the input end of the brain microdialysis probe 5 through the first hose 13, and the first collector port is connected to the output end of the brain microdialysis probe 5 through the second hose 14, so as to collect the brain microdialysis samples in the dual-channel cooling microcollector 7, improving the convenience of use of the blood-brain synchronous microdialysis sampling device applicable to freely moving rats under aerosol exposure.

[0026] As Figure 1As shown, it further includes a third hose 15 and a fourth hose 16. A second probe interface and a second collector port are also provided at the top of the aerosol exposure chamber 2. One end of the third hose 15 is connected and installed at the second Ringer's solution outlet 10. The third hose 15 extends into the hollow cavity through the second probe interface. The other end of the third hose 15 is connected and installed at the output end of the blood microdialysis probe 6. One end of the fourth hose 16 is connected and installed at the second collection port 12. The fourth hose 16 extends into the hollow cavity through the second collector port. The other end of the fourth hose 16 is connected and installed at the output end of the blood microdialysis probe 6. In this embodiment, the specifications of the third hose 15 and the fourth hose 16 are 6.35×10.16 mm (inner diameter × outer diameter). The second Ringer's solution outlet 10 is connected to the input end of the blood microdialysis probe 6 through the third hose 15, and the second collector port is connected to the output end of the blood microdialysis probe 6 through the fourth hose 16, so as to collect the blood microdialysis sample in the dual-channel cooling microcollector 7, improving the convenience of use of the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure.

[0027] As Figure 1 shown, a particulate matter concentration monitoring port is also provided at the top of the aerosol exposure chamber 2. The particulate matter concentration monitor 3 is sealed and installed at the particulate matter concentration monitoring port to monitor the particulate matter concentration in the hollow cavity. In this embodiment, by sealing and installing the particulate matter concentration monitor 3 at the particulate matter concentration monitoring port, the particulate matter concentration after aerosol exposure in the hollow cavity is monitored, improving the convenience of use of the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure.

[0028] As Figure 1 shown, the aerosol exposure chamber 2 further includes a first side surface. An air extraction port is provided on the first side surface. The air extraction pump 8 is connected to the hollow cavity through the air extraction port. In this embodiment, the air extraction pump 8 can extract the used aerosol from the aerosol exposure chamber 2 through the air extraction port, improving the convenience of use of the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure.

[0029] As Figure 1 shown, the aerosol exposure chamber 2 further includes a second side surface opposite to the first side surface. An aerosol input port is provided on the second side surface. The aerosol in the aerosol generator 1 enters the hollow cavity through the aerosol input port. In this embodiment, the aerosol generator 1 conveniently inputs the aerosol into the hollow cavity through the aerosol input port, improving the convenience of use of the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure.

[0030] As Figure 1As shown, the first hose 13 and the second hose 14 are both PE hoses. In this embodiment, the PE hose has good flexibility, reliable connection, good impact resistance, and corrosion resistance, which improves the service life of the first hose 13 and the second hose 14, and further improves the service life of the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure.

[0031] As Figure 1 shown, the third hose 15 and the fourth hose 16 are both PE hoses. In this embodiment, the PE hose has good flexibility, reliable connection, good impact resistance, and corrosion resistance, which improves the service life of the third hose 15 and the fourth hose 16, and further improves the service life of the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure.

[0032] As Figure 1 shown, the aerosol generator 1 includes a micro air compressor 17. In this embodiment, the micro air compressor 17 generates compressed air and passes it through a narrow nozzle at high speed. According to the Venturi effect, a negative pressure is generated around the nozzle, and the liquid solution is brought into the high-speed air flow and sprayed to form aerosol particles, which are continuously and stably ejected, providing continuous and stable aerosol for the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure, and improving the convenience of use of the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure.

[0033] In an embodiment of the present utility model, the material of the aerosol exposure chamber 2 is an acrylic glass plate. The acrylic glass plate has the characteristics of high transparency, good weather resistance, easy processing, and environmental protection, which improves the convenience of use of the blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure.

[0034] In an embodiment of the present utility model, first, the brain microdialysis probe 5 and the blood microdialysis probe 6 are respectively implanted into the brain region of interest and the jugular vein blood vessel. After the operation, the experimental rats are placed in the aerosol exposure chamber 2 and allowed to recover for at least 24 h while adapting to the new environment; before aerosol exposure, the brain microdialysis probe 5 and the blood microdialysis probe 6 are connected to the dual-channel cooling microcollector 7, and the injection pump 4 is turned on and balanced for two hours; then, the aerosol exposure chamber 2 is connected to the aerosol generator 1, and at the same time, the aerosol generator 1 and the air extraction pump 8 are turned on to ensure the stability of the aerosol concentration in the hollow cavity, and the awake and freely moving animals are exposed to the nicotine aerosol environment. The blood dialysis sample and the brain microdialysis sample are continuously collected through the dual-channel cooling microcollector 7. By analyzing the blood dialysis sample and the brain microdialysis sample, the regulatory effect of nicotine inhalation on animal neurotransmitters can be more truly reflected.

[0035] The present utility model provides a blood-brain synchronous microdialysis sampling device applicable to freely moving rats under aerosol exposure, which includes an aerosol generator 1, an aerosol exposure chamber 2, a particulate matter concentration monitor 3, an infusion pump 4, a brain microdialysis probe 5, a blood microdialysis probe 6, a dual-channel cooling microcollector 7, and an air extraction pump 8. When in use, the brain microdialysis probe 5 and the blood microdialysis probe 6 are respectively implanted into the brain and jugular vein of an animal in advance. The infusion pump 4, the brain microdialysis probe 5, the blood microdialysis probe 6, and the dual-channel cooling microcollector 7 are connected. First, the infusion pump 4 is turned on. After a period of equilibration, the aerosol generator 1 and the air extraction pump 8 are then turned on for a period of time to ensure the stability of the aerosol concentration in the aerosol exposure chamber 2. When the animal is awake and freely moving, it is exposed to a nicotine aerosol environment, and the dual-channel cooling microcollector 7 continuously collects brain microdialysis samples and blood microdialysis samples. By analyzing the blood dialysis samples and the brain microdialysis samples, the regulatory effect of nicotine inhalation on animal neurotransmitters can be more realistically reflected.

[0036] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present utility model and are not intended to limit them. Although the present utility model has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments or perform equivalent replacements for some of the technical features. However, such modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the various embodiments of the present utility model.

Claims

1. A blood-brain synchronous microdialysis sampling device suitable for freely moving rats under aerosol exposure, characterized in that: It includes an aerosol generator, an aerosol exposure chamber, a particle concentration monitor, an injection pump, a brain microdialysis probe, a blood microdialysis probe, a dual-channel cooling micro-collector, and an air pump, wherein: A hollow cavity is provided in the aerosol exposure cavity, and the hollow cavity is used to place the animal; The brain microdialysis probe is used for implantation into the brain region of the animal, and the blood microdialysis probe is used for implantation into the jugular vein of the animal; The injection pump comprises a first Ringer's solution output port and a second Ringer's solution output port, wherein the first Ringer's solution output port is connected to the input end of the brain microdialysis probe, and the second Ringer's solution output port is connected to the input end of the blood microdialysis probe; The dual-channel cooling micro-collector comprises a first collecting port and a second collecting port, wherein the first collecting port is connected to the output end of the brain microdialysis probe, and the second collecting port is connected to the output end of the blood microdialysis probe; The suction port of the air pump, the particle concentration monitor, and the output port of the aerosol generator are all connected to the hollow cavity.

2. The blood-brain synchronous microdialysis sampling device suitable for freely moving rats under aerosol exposure according to claim 1, characterized in that: It also includes a first hose and a second hose. The top of the aerosol exposure cavity is provided with a first probe interface and a first collector port. One end of the first hose is connected and installed at the first Ringer's solution output port, the first hose extends into the hollow cavity through the first probe interface, and the other end of the first hose is connected and installed at the input end of the brain microdialysis probe; one end of the second hose is connected and installed at the first collecting port, the second hose extends into the hollow cavity through the first collector port, and the other end of the second hose is connected and installed at the output end of the brain microdialysis probe.

3. The blood-brain synchronous microdialysis sampling device suitable for freely moving rats under aerosol exposure according to claim 1, characterized in that: It also includes a third hose and a fourth hose. A second probe interface and a second collector port are provided on the top of the aerosol exposure cavity. One end of the third hose is connected and installed at the second Ringer's solution output port, and the third hose extends into the hollow cavity through the second probe interface. The other end of the third hose is connected and installed at the output end of the blood microdialysis probe. One end of the fourth hose is connected and installed at the second collecting port, and the fourth hose extends into the hollow cavity through the second collector port. The other end of the fourth hose is connected and installed at the output end of the blood microdialysis probe.

4. The blood-brain synchronous microdialysis sampling device suitable for freely moving rats under aerosol exposure according to claim 1, characterized in that: A particle concentration monitoring port is also provided on the top of the aerosol exposure cavity, and the particle concentration monitor is sealed and installed on the particle concentration monitoring port to monitor the particle concentration in the hollow cavity.

5. The blood-brain synchronous microdialysis sampling device suitable for freely moving rats under aerosol exposure according to claim 1, characterized in that: The aerosol exposure cavity further comprises a first side surface, a suction port is formed on the first side surface, and the suction pump is connected to the hollow cavity through the suction port.

6. The blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure according to claim 5, characterized in that: The aerosol exposure cavity further includes a second side surface arranged opposite to the first side surface, and the second side surface is provided with an aerosol input port, and the aerosol in the aerosol generator enters into the hollow cavity through the aerosol input port.

7. The blood-brain synchronous microdialysis sampling device suitable for freely moving rats under aerosol exposure according to claim 2, characterized in that: The first hose and the second hose are both PE tubes.

8. The blood-brain synchronous microdialysis sampling device suitable for freely moving rats under aerosol exposure according to claim 3, characterized in that: The third hose and the fourth hose are both PE tubes.

9. The blood-brain synchronous microdialysis sampling device for freely moving rats under aerosol exposure according to claim 1, characterized in that: The aerosol generator comprises a micro air compressor.

10. The blood-brain synchronous microdialysis sampling device suitable for freely moving rats under aerosol exposure according to claim 1, characterized in that: The aerosol exposure cavity is made of an acrylic glass plate.

Images