JP2012179271A - Measuring device of brain activity, respiration and blood pressure for small animal - Google Patents

Abstract

PROBLEM TO BE SOLVED: To simultaneously measure electrical activity of brain, the amount of intracerebral biochemical secretion, blood pressure and respiration of an awakeful animal.SOLUTION: The measuring device includes a screw 11 and a support 12 for fixing a head of an animal to which a head fixing accessory 26 is mounted in advance. A respiration measuring device sensor part 21 of a respiration measuring device body monitor part 22 is mounted to a neck of the animal, invasive blood pressure measurement from an arterial catheter 23 previously indwelled is prepared so that the head of the awakeful animal is fixed to measure the blood pressure and the respiration is simultaneously measured, and a recording electrode 28 and a microdialysis probe 29 are inserted into the brain of the animal whose head is fixed. Consequently, the electrical activity of the brain, the amount of intracerebral biochemical secretion, the blood pressure and the respiration can be simultaneously measured.

Description

  The present invention relates to a method for measuring brain activity, respiration, and blood pressure in awake small animals.

  Conventionally, a simple method for measuring the blood pressure of a test animal (mainly a rat) at the time of awakening was performed by using a non-invasive sphygmomanometer and wrapping a cuff around the tail. At that time, it is necessary to immobilize the body and tail of the subject animal in some way in order to measure blood pressure stably and stably with little stress. For this purpose, a body fixing tool 31 as shown in FIG. The sphygmomanometer body 33 is connected to a blood pressure measurement cuff 32. The animal was confined in the body fixing tool 31, the tail was taken out, the blood pressure was measured with the blood pressure measurement cuff 32 attached while the tail was fixed to the tail fixing tool 34.

  A simple method for monitoring respiration is to wrap a respiration measurement strain sensor 35 around the body of a test animal under anesthesia, for example, as shown in FIG. There is known a method of detecting the movement connected to the. This method was performed exclusively in anesthetized animals, and in awake animals, measurement was not possible due to movements other than breathing of the animal caused by attaching the strain sensor 35 for respiratory measurement.

  As a method for measuring brain activity of a test animal at awakening, a method for measuring brain electrical activity and a method for measuring the amount of biochemical secretions such as neurotransmitters and neuromodulators in the brain are known. When measuring the electrical activity of the brain, a measurement electrode is chronically attached to the brain of the subject animal in advance, and then the activity of nerve cells around the recording electrode under free action is recorded. At that time, attempts have been made to efficiently record the activity of a plurality of nerve cells by using a multi-channel electrode or by inserting a plurality of electrodes into the brain and moving each electrode independently. However, even if the nerve cells around the recording electrode can be recorded, it is often difficult to measure stably for a long time because of the free action, or the nerve cells around the recording electrode cannot be recorded in the first place. On the other hand, when measuring the amount of biochemical secretion, as shown in FIG. 4, a microdialysis probe 29 is inserted into the brain in advance, and a perfusate is passed through the probe, and the semipermeable membrane of the probe is attached. The biochemical secretions were collected through the medium, and the collected liquid was weighed using an analyzer such as high performance liquid chromatography or a mass spectrometer. Two tubes for input and output are required to collect the perfusate, and the biochemical secretions in the brains of awake small animals can be measured by allowing the animals to move freely with these tubes. I was able to. In order to realize this, it was necessary to prevent the two tubes from being entangled during free movement, and a two-tube sieve 41 was used.

JP 2003-190191 A Japanese Patent Application Laid-Open No. 2001-078608

  When investigating physiological phenomena in experimental animals as models, it is desirable to be able to observe normal phenomena.

  By simply combining the techniques described in the background art above, it is difficult to simultaneously measure normal brain electrical activity, brain biochemical secretion, respiration, and blood pressure. The reason is as follows.

  1. In the blood pressure measurement method, since the body is fixed and held, it is difficult to attach a respiratory monitor sensor to a portion other than the exposed tail, and a recording electrode for recording brain activity is attached to the head. This is also difficult due to the structure.

  2. The respiratory monitoring method described in the prior art, which can be measured in anesthetized animals, and the blood pressure measurement method using a non-invasive blood pressure meter described in the prior art result in unnecessary irritation and stress in awake animals. In addition to being a hindrance to measuring the brain activity of the time, the items of brain electrical activity, respiration, and blood pressure cannot be accurately measured due to noise caused by body movement.

  3. For example, in order to record brain activity in response to sensory stimuli, it is necessary to identify the desired response by inserting a recording electrode into the brain with very high accuracy. It is difficult to identify the neural activity that responds to the target while measuring respiration and blood pressure in freely moving animals.

  4). Under free action, the microdialysis method alone can collect perfusate and analyze the amount of biochemicals, but it cannot be used to record brain electrical activity. This is because, although a sieve corresponding to two tubes exists and can be used, if a third wire is required, there is no sieve that can connect a total of three tubes of two tubes and wires.

  An object of the present invention is to solve the above-described conventional problems, and to achieve simultaneous measurement of brain electrical activity, biochemical secretion, blood pressure, and respiration in a normal test animal.

  In order to solve the above-mentioned conventional problems, the brain activity blood pressure respiration measuring device for small animals of the present invention is a device for simultaneously measuring the brain activity, blood pressure and respiration of a small animal, and stably and accurately measures the brain activity. The head has a head fixing screw 11, a support 12, and a head fixing auxiliary tool 26, and a recording electrode 28 for measuring the electrical activity of the brain is attached to the brain, and the biochemistry in the brain A microdialysis probe 29 is attached to the brain to measure the amount of secretory secretion, and a respiratory measurement device sensor 21 for measuring the respiration rate of the rat is attached to the dorsal neck and is derived from the femoral artery or abdominal aorta. By connecting a pressure transducer 24 for measuring blood pressure to the arterial catheter 23 and placing it outside the body, it simultaneously measures the electrical activity of the brain of the awake rat, the amount of biochemical secretion in the brain, and the respiration and blood pressure. That is a device.

  According to the respiratory activity blood pressure measuring device for small animals of the present invention, the local brain activity by the normal electrical activity recording of the awake state of the small animals including the rat, and the wide range of brain activities by the biochemical secretion amount measurement Blood pressure and respiration can be measured simultaneously. Furthermore, the type of active nerve cell can be estimated from the analysis result of the amount of biochemical secretion.

(A) A view of a head-fixing portion of a brain activity respiratory blood pressure measurement device for small animals according to an embodiment of the present invention as viewed from the front. (A) The brain activity respiratory blood pressure measurement device for small animals according to an embodiment of the present invention. The figure which looked at the part for head fixation from the side (c) The figure which looked at the part for head fixation of the brain activity respiratory blood pressure measuring device for small animals in embodiment of this invention from the upper surface (D) Side view of the infrared light detection type respiration measurement device, open blood pressure measurement device, recording electrode for recording brain electrical activity, and microdialysis probe in the embodiment of the present invention. 1 is a front view of an infrared light detection type respiratory measurement device, an open blood pressure measurement device, a recording electrode for recording electrical activity of a brain, and a microdialysis probe according to an embodiment of the invention. Diagram of conventional non-invasive blood pressure measurement method and respiration measurement method using strain sensor A diagram of a conventional microdialysis in the brain under the free movement of a subject animal, in which a microdialysis probe 29 displaying an arrow indicating the flow direction of the perfusate and a cannula sieve 41 are combined.

  Embodiments of the present invention will be described below with reference to the drawings.

(Embodiment)
Embodiments of the present invention will be described below.

  First, the head fixing auxiliary tool 26 is mounted on a small animal (such as a rat) in advance, and is fixed to the column 12 with the head fixing screw 11 via the head fixing auxiliary tool 26 of the animal. If the head-fixing auxiliary tool 26 is mounted horizontally on the head of the small animal, the small animal can fix the head in the same direction every time thereafter. FIG. 2 schematically shows a state where a small animal is attached to a fixture. By attaching a small animal to the head fixture several times, even an awakened animal can be attached smoothly.

  When the respiration measuring device sensor unit 21 is worn, shaving is performed from the back side of the small animal to the ventral side so that the sensor is in close contact with the skin. Then, a gel that fills the space between the sensor and the portion from the back side to the ventral side of the neck of the small animal is applied to the sensor unit. The output of the respiration measurement device sensor unit 21 is sent to the respiration measurement device body monitor unit 22 through a cable. The respiration measuring device sensor unit 21 is mounted by sandwiching the neck of a small animal, but naturally does not hinder the movement and respiration of the neck.

  The blood pressure measuring device is of the open type. An arterial catheter 23 is placed in advance in the femoral artery of a small animal and is led out of the body from the back side through a subcutaneous tunnel. The end of the catheter is connected to a pressure transducer 24 outside the body. The output of the pressure transducer 24 is input to the sphygmomanometer main body display unit 25.

  In order to measure brain activity, a necessary minimum hole for inserting the recording electrode and the microdialysis probe 29 is made in the skull of the animal in advance, and a guide tube for inserting the microdialysis probe 29 is attached. Keep it fixed.

  When measuring brain activity, a mask 27 is attached to a small animal, ventilated, a microdialysis probe 29 is inserted through a guide tube, and when the target site is reached, the perfusate is allowed to flow for 2 hours. The arrow of the microdialysis tube 29 indicates the direction in which the perfusate flows. The fluid perfused in the brain after 2 hours is collected and used for later analysis. Thereafter, the recording electrode 28 is inserted into the hole of the skull that has been opened beforehand. The arrow extending from the recording electrode 28 indicates the flow of the signal of the brain activity to be measured, and the point leads to the recording device. The mask 27 is mounted so as to cover the animal's nose and can present any gas. The odor stimulus is presented to the nose of the small animal through the mask 27, the breathing is performed through the respiration measuring device, the blood pressure is measured through the blood pressure measuring device, and the brain activity is recorded while adjusting the position of the recording electrode of the brain. To do.

  According to such a component, it is possible to attach a respiration sensor from the back of the neck and a pressure sensor to an arterial catheter guided from the femoral artery by simply fixing the head of the animal. Brain activity, respiration and blood pressure can be measured simultaneously.

  The head fixing auxiliary tool 26 may be fixed to the column 12 by pinning or vise fixing in addition to screwing.

  The small animals may be rodent small animals such as rats, mice, guinea pigs, hamsters, and gerbils.

  One post or two or more screws may be used for screwing the post 12.

  The respiratory measurement device may be a pulse oximeter.

  The respiratory measurement device may be a pulse wave sensor.

  Although it has been described that the arterial catheter is placed in the femoral artery, it may be placed in the abdominal aorta.

  Instead of the odor stimulus via the mask 27, a visual stimulus presented to the eyes, a taste stimulus presented to the tongue, an auditory stimulus presented to the ear, or a somatosensory stimulus for stimulating the sinus hair may be used.

  According to the cerebral activity blood pressure respiration measuring apparatus for small animals of the present invention, by simultaneously measuring the cerebral activity and blood pressure and respiration of an awake small animal, anyone can easily determine the normal brain activity and physiological state of the animal. Therefore, it is possible to examine the electrical response of the brain when a stimulus or manipulation is applied to an experimental animal, the amount of biochemical secretion in the brain, the blood pressure, and the physiological response of breathing.

DESCRIPTION OF SYMBOLS 11 Head fixing screw 12 Support | pillar 13 Base 21 Respiration measuring device sensor part 22 Respiration measuring device main body monitor part 23 Arterial catheter 24 Pressure transducer 25 Sphygmomanometer main body display part 26 Head fixing auxiliary tool 27 Mask 28 Recording electrode 29 Microdialysis Probe 31 Body fixing device 32 Blood pressure measurement cuff 33 Blood pressure measurement device main body 34 Tail fixing device 35 Respiratory measurement strain sensor 36 Respiration measurement device main body 41 Cannula sieve

Claims (2)

A device for measuring brain activity, respiration and blood pressure in small animals,
Having an auxiliary tool to fix the head,
The head is fixed through the assisting device, and the device can rest the body of an awake animal in a resting state, presenting sensory stimulation to the small animal,
Measure brain electrical activity from the head of the small animal,
Measure the amount of brain biochemical secretions from the head of the small animal,
Measure respiration from the infrared reflected light of the neck of the small animal,
An apparatus for measuring cerebral activity, blood pressure, and respiration of an awake small animal, wherein the blood pressure is measured in an invasive manner from an artery of the small animal.   The apparatus according to claim 1, wherein the sensory stimulus is visual, auditory, tactile sense including sinus hair, olfactory sense, taste sense, temperature, and pain stimulus.

Images