JP2006320221A - Method for evaluation of motor function disorder, use of the method and motor function evaluation device therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for evaluating motor function with a treadmill in high sensitivity and a device for the evaluation method. <P>SOLUTION: The motor function of human or non-human vertebrates is evaluated by counting the number of normal walk steps or slip troubles of the foot caused by the failure in normal walk during the walking or running of an examinee on the treadmill. The motor function evaluation device is provided with a treadmill, a monitoring device for monitoring the walking or running of the examinee on the treadmill, and a counting device to count the number of normal walk steps or slip troubles of the foot caused by the failure in normal walk of the examinee on the treadmill. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a method for evaluating a vertebrate motor dysfunction, a method for using the method, and a motor function evaluating apparatus for use in the method.

  Conventionally, in order to measure the motor function of a subject and evaluate the motor function, the running time, the running distance, and the endurance when a subject is forced to exercise by using a treadmill. It has been done to measure. Until now, the state of disease (for example, motor function disorder due to stroke or spinal cord injury) has been evaluated using such a treadmill motor function measurement method (for example, Non-Patent Document 1, Non-patent Document 1, (See Patent Document 2).

Such conventional motor function measurement methods evaluate the motor function by observing the walking of the subject with the naked eye, and therefore cannot evaluate the motor function objectively, and the evaluation lacks quantitativeness. Had. In order to solve this problem, an apparatus for measuring the walking of a subject has been developed so far (see, for example, Patent Document 1 and Patent Document 2).
Japanese Patent Laid-Open No. 10-228540 JP 2003-250780 A Arch.Phys.Med.Rehabil. (2003) 84: 1458-65 Science. (1998) 279: 320

  For example, there is a rotarod treadmill as a device for measuring the motor function of a laboratory animal such as a mouse or a rat. A motor function measuring method using this device is a subject running on the surface of a rotating rotor shaft. However, it was a method to detect the endurance time of the subject by detecting it with a photo beam when falling from the surface of the axis, but the development of a measurement method that can measure motor function with higher sensitivity is expected. Yes.

  Accordingly, an object of the present invention is to provide a method capable of evaluating motor function with higher sensitivity using a treadmill, and an apparatus for quantitative measurement using the method.

  When a test of motor function evaluation using a treadmill is performed on a subject, the subject is walking or running on a movable floor on the treadmill, and therefore falls due to an impact at the start of walking or running, Alternatively, except for problems such as slipping during walking or running, if the subject's motor function declines, normal walking or running on the floor surface becomes impossible, and an action of sliding the foot occurs. The present inventors focused on the action of sliding a foot without being able to perform normal walking or normal running while the subject is walking or running on a treadmill, and by measuring the number of times the foot was slid, Invented a method for evaluating motor function with higher sensitivity than the method for evaluating motor function.

  That is, the motor function evaluation method according to the present invention is a method for evaluating motor function impairment in a human or non-human vertebrate, and the motor function evaluation method is a method in which a subject normally walks or runs normally on a treadmill. It is characterized by measuring the number of times the user has slipped without being able to.

  The motor dysfunction is, for example, a disorder caused by a neurological disease.

  The treadmill is, for example, a rotarod treadmill.

  The method for diagnosing a disease associated with motor dysfunction according to the present invention is a method for diagnosing a disease associated with motor dysfunction in a human or a non-human vertebrate, wherein the subject is normally walking or moving on a treadmill. It is characterized by measuring the number of times the user slipped without being able to run normally.

  Furthermore, the method for evaluating treatment for motor dysfunction according to the present invention is a method for evaluating treatment for motor dysfunction in a human or non-human vertebrate having motor dysfunction, which is performed on a treadmill. And measuring the number of times the subject slips his / her foot without normal walking or normal running.

  Further, the method for evaluating the effectiveness of the therapeutic agent according to the present invention is a method for evaluating the effectiveness of the therapeutic agent for the motor dysfunction in a human or non-human vertebrate having a motor dysfunction. The method is characterized in that the number of times the subject slides on the treadmill without being able to normally walk or run normally is measured.

  Furthermore, the method for evaluating the safety of a drug according to the present invention provides the safety of the drug when administering a drug capable of developing motor dysfunction as an adverse event (for example, a side effect) to a human or a non-human vertebrate. A safety evaluation method for evaluating, characterized in that the degree of the motor dysfunction is evaluated by measuring the number of times the subject slides on the treadmill without normal walking or normal running. To do.

  A motor function evaluation apparatus according to the present invention is a motor function evaluation apparatus for evaluating a motor function of a vertebrate, and the motor function evaluation apparatus includes a treadmill and a walking of a subject on the treadmill. Alternatively, it includes a monitoring device for monitoring running and a measuring device for measuring the number of times the subject slides on the treadmill without normal walking or normal running.

  The monitoring device may include, for example, a detection device for detecting that the subject has slipped his / her foot.

  The detection device may include, for example, an infrared sensor or a video camera.

  Furthermore, the method for screening a therapeutic agent according to the present invention caused the subject to slide on the treadmill without normal walking or running on a human or non-human vertebrate having a motor dysfunction. It is a method of screening an effective therapeutic agent for the motor dysfunction using a method for evaluating the effectiveness of the therapeutic agent for motor dysfunction characterized by measuring the number of times.

  The term “treadmill” described in the present specification refers to a device that has a movable floor surface and is made so that a subject can walk or run against the moving floor surface. The treadmill that can be used in the present invention also includes a rotarod toledo mill. The “rotor rod treadmill” is a rotating rotor, and the subject rotates in the direction of rotation on the surface of the shaft around which the rotor rotates. This is a device configured to be able to walk or run against the above.

  According to the present invention, it is possible to provide a method capable of evaluating a motor function with higher sensitivity using a treadmill, and an apparatus for quantitative measurement using the method.

  Hereinafter, the present invention will be described specifically and in detail with reference to examples, but the present invention is not limited thereto.

  The objects, features, advantages, and ideas of the present invention will be apparent to those skilled in the art from the description of the present specification, and those skilled in the art can easily reproduce the present invention from the description of the present specification. it can. The embodiments and specific examples of the invention described below show preferred embodiments of the present invention and are shown for illustration or explanation, and the present invention is not limited to them. It is not limited. It will be apparent to those skilled in the art that various modifications can be made based on the description of the present specification within the spirit and scope of the present invention disclosed herein.

== Motor function evaluation method ==
The motor function evaluation method of the present invention evaluates motor function disorder by measuring the number of times the subject “slid his / her foot” when the subject normally walks or runs normally on a treadmill. As used herein, the treadmill may have any form as long as the apparatus has a movable floor surface and is constructed so that the subject can walk or run against the moving floor surface. Typically, the floor surface is configured in a belt shape, and the floor surface is configured to move when the belt moves. In addition, a rotor rod treadmill configured to rotate a rotor having a shape in which a cylinder is tilted so that the subject can walk or run on the surface of the rotor against the direction of rotation is also evaluated for motor dysfunction. obtain. The rotarod treadmill is a device that walks or travels on a curved surface called the surface of the rotor, and is more preferable because it is more difficult to walk or travel than on a flat surface, and has high detection sensitivity for motor dysfunction.

  The subject is, for example, a human or a non-human vertebrate individual. The subject is placed on the treadmill and the floor surface is operated. Next, the subject is forced to walk or run against the moving direction of the floor surface. It is preferable to set the rotation speed so that the subject does not fall. For example, the rotation speed in the embodiment is set to 5-6 rpm in the case of a brain contusion model. Furthermore, because of the guidance, it is possible to increase the sensitivity of motor function evaluation. Since the subject slides his / her foot when there is a motor dysfunction, in this method, the number of times of sliding his / her foot per unit time is measured. In the example, the number of times of sliding the foot per minute was measured. Here, “sliding a foot” includes, but is not limited to, the movement of the lower limb caused by the subject falling, slipping, tripping, or tangling the lower limb. If it falls off the rotor during measurement, you can start over. Next, the motor function of the subject is evaluated based on the measured value. As a motor function evaluation method, when the number of times of sliding the foot per unit time is increased from the reference value, it is evaluated that the motor function disorder is present or the motor function disorder originally possessed is worsening. On the contrary, when the number of times is less than the reference value, it is evaluated that the motor dysfunction is not present or the motor dysfunction originally possessed is reduced. It can be determined that the more the number of times the foot is slid per unit time, the more severe motor dysfunction is. Here, the reference value as a comparison reference may be, for example, the value of the motor function of a normal individual, or may be the value of the motor function when there is no motor function disorder of the same subject. Without limitation, the value of the motor function at an arbitrary time point in the same subject can be used.

== Diagnosis of diseases with motor dysfunction ==
The motor function evaluation method of the present invention can be used in the diagnosis of diseases having motor function disorders in humans or non-human vertebrates.

  The motor dysfunction to be evaluated is not particularly limited as long as it is a motor function disorder, and may be a nervous system disorder or a muscular system disorder. Diseases that cause motor dysfunction include cerebrovascular disorders, spinal vascular disorders, brain and spinal cord tumors, neuropathy caused by spinal diseases, infectious diseases, dementia diseases, metabolic / toxic diseases, basal ganglia degenerative diseases Cerebral cerebellar degenerative disease, motor neuron disease, peripheral nerve disease, demyelinating disease, muscle disease, and congenital abnormalities, specifically, gait disorder, standing disorder, convulsions, chorea, ballism, dystonia, Epilepsy, myoclonus, tic, cerebral hemorrhage, cerebral thrombosis, cerebral embolism, cerebral infarction, stroke, cerebral ischemia, Binswanger disease, hemiplegia, limb paralysis, ataxia, spinal cord infarction, spinal vein infarction, brain tumor, spinal cord tumor, encephalitis , Brain abscess, tuberculoma, Alzheimer's disease, Parkinson's disease, dementia, Wilson's disease, liver lens nuclear degeneration, Menkes' disease, amyloidosis, sphingolipidosis, amino acid metabolism disorder, vitamin Diseases such as, but are not limited to, diseases such as hypoxia, alcoholism, alcoholic neuropathy, organic solvent poisoning, summon, progressive supranuclear paralysis, and striatal nigra degeneration.

  The present invention is particularly useful when diagnosing a disease that exhibits mild motor dysfunction that is difficult to determine with the naked eye. For example, the motor function of the subject is measured according to the motor function evaluation method of the present invention, the motor function value of healthy animals or other reference values (for example, the motor function for each disease is set in advance, and the value is scored. ), It can be determined whether or not the subject has a motor dysfunction. When diagnosing a disease, the motor function evaluation method of the present invention may be used in combination with another examination (for example, an image examination such as CT or MRI).

== Evaluation of treatment for diseases with motor dysfunction ==
The method of evaluating treatment for diseases with motor dysfunction in humans or non-human vertebrates measures the number of times the foot is slipped per unit time, and when this value is lower than before treatment, When this value is the same or increased as before treatment, it is judged that there is no treatment effect. In this way, the evaluation method of the present invention can determine whether or not the treatment method being used is effective. The treatment here may be treatment that does not require medication such as rehabilitation, or administration of a therapeutic agent.

  In addition, for the treatment in which a therapeutic agent is administered, the effectiveness of the therapeutic agent can be evaluated using the motor function evaluation method of the present invention. The method for evaluating the effectiveness of a therapeutic drug is to measure the number of times the foot is slipped per unit time, and when this value decreases from the time of therapeutic drug administration, it is determined that the therapeutic drug is effective. When the drug is the same as or increased from the time of drug administration, the therapeutic drug is judged to be ineffective. It should be noted that this evaluation method can be used at any time after administration of the therapeutic agent, and may be performed over time, several minutes, several hours, several days, or several years later.

  The therapeutic agent used may be any drug that can treat motor dysfunction. The therapeutic agent used can also be administered orally or parenterally (eg, intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous, or intradural). Yes, as long as it is an effective dosage and appropriate dosage form, any dosage form and dosage form can be used including oral preparations and inhalants. In the examples, IL-12 was used.

  Furthermore, by evaluating the effectiveness of the therapeutic agent as described above using the motor function evaluation method of the present invention, it is possible to set a dose for the therapeutic agent. For example, by correlating the dose of the target therapeutic agent with the motor function value of the subject after administration of the therapeutic agent measured according to the method for evaluating motor function of the present invention, the motor function is improved even if the therapeutic agent is reduced. The dose of therapeutic agent can be set, such as determining the minimum dose that does not decrease.

  Further, by using the motor function evaluation method of the present invention, it is possible to measure the difference in the sensitivity of the therapeutic agent due to individual differences, sex differences, species differences or age differences, and set the dosage of the therapeutic agent considering the difference in sensitivity. can do.

== Evaluation of drug safety after drug administration ==
The motor function evaluation method of the present invention can be used for evaluating the safety of a drug when administering a drug capable of developing motor function disorder as an adverse event such as a side effect to a human or a non-human vertebrate.

  The drug safety evaluation method measures the number of times the foot is slipped per unit time, and when this value is the same as or decreased from the time of drug administration, this drug is judged to be safe, and this value is The drug is considered harmful when it is increased from the time of administration. Note that this evaluation method can be used at any time after drug administration, and may be performed over time, several minutes, several hours, several days, or several years later.

  The drug for which safety is evaluated may be any drug that can be administered to a subject. The route of administration of the drug may be oral or parenteral (eg, intradermal, subcutaneous, intramuscular, intraperitoneal, intravenous, or intradural). The dosage form of this drug may be any dosage form including oral preparations and inhalants, and any dosage can be used.

  For example, when a subject uses a plurality of drugs in combination, a drug-drug interaction that expresses a motor dysfunction that is simply not expected from the pharmacological action of the drug can be found according to the motor function evaluation method of the present invention. .

  In addition, when a barbituric acid derivative, meprobamate, chlordiazepoxide, diazepam, nitrazepam, phenytoin, isoniazid, ethionamide, MAO inhibitor, etc., known as drugs that cause neuropathy are administered to the subject, the subject has motor dysfunction It can be judged using the motor function evaluation method of this invention whether the side effect is expressed.

  Furthermore, even when an unknown drug is administered to a subject, it can be found using the motor function evaluation method of the present invention whether or not the subject exhibits side effects of motor dysfunction.

== Motor function evaluation device ==
The motor function evaluation device used in the present invention includes a monitoring device and a measurement device in addition to the treadmill. The monitoring device is a device that monitors the movement of the subject moving on the treadmill, and preferably includes a detection device that mechanically detects the movement of the subject sliding the foot. Examples of the detection device include an infrared sensor or a moving camera. In addition, the measurement device refers to a device that measures the number of times the subject slides his / her foot detected by the monitoring device in conjunction with the monitoring device.

  For example, FIG. 2A shows a configuration diagram of a motor function evaluation apparatus in which the detection device described above is an infrared sensor. 1A shows the entire rotarod treadmill, and FIG. 1B shows an enlarged view of the vicinity of the rotation axis when the rotarod treadmill is viewed from the front. As shown in FIG. 2A, the motor function evaluation apparatus includes a rotarod treadmill (1), an infrared transmitter (3) that transmits infrared rays (2) in a direction parallel to the moving direction of the floor, and a subject when receiving infrared rays. The measuring device (5) etc. which can analyze each data at the time of infrared non-reception blocked by the foot (4). First, the subject is placed on the surface of the shaft (6) of the rotarod treadmill, and the subject is moved by rotating the rotor. During this time, when the subject slides the foot (4) on the surface of the rotor shaft, the foot (4) blocks the infrared ray (2) transmitted from the infrared transmitter (3). By measuring the number of times the infrared ray is blocked by the measuring device (5), the motor function of the subject can be measured. In FIG. 2A, infrared rays are transmitted from the back of the rotor shaft (6). However, when the shaft (6) of the rotarod treadmill is transparent, infrared rays are transmitted from the front of the rotor shaft, You may detect the operation | movement which slipped the leg | foot.

  FIG. 2B shows a configuration diagram of a motor function evaluation apparatus in which the detection apparatus described as an embodiment of the present invention is a moving image camera. The motor function evaluation apparatus in the present embodiment includes a rotarod treadmill (1), a video camera (7), a measurement apparatus (8), and the like. First, the subject is placed on the surface of the shaft (6) of the rotarod treadmill, and the subject is moved by rotating the rotor. During this time, the moving image camera (7) is always operated, and the movement of the subject moving on the rotarod treadmill is photographed from behind the rotor shaft (6). The measuring device (8) includes a system for converting moving image data captured by a moving image camera into still image data, a system for accumulating the still image data, a system for analyzing the still image data, and the like. Then, the number of times that the subject slides the foot from the video data is measured. If more precise measurement is desired, the number of times that the subject has slid his / her foot may be manually measured by reproducing an image taken with a video camera. When the rotor axis is transparent, the walking or running of the subject may be photographed with a video camera from the front of the rotor axis.

== Method for screening effective therapeutic agent for motor dysfunction ==
In order to screen a human or non-human vertebrate for an effective therapeutic agent for motor dysfunction, the motor function evaluation method of the present invention can be used.

  First, a novel compound that is a candidate for a therapeutic drug for motor dysfunction is administered to an animal model having a motor function disease, and the number of times the foot is slid per unit time is measured. If the number of times decreases after administration compared to before administration, it can be judged that this compound was effective against motor dysfunction. In addition, when this value is smaller than when a known compound is administered, it can be determined that the novel compound is more effective than the known compound. Further, by observing the effect on motor dysfunction by changing the concentration of this compound, the concentration dependence of the effect of this compound can also be clarified. In addition, when motor dysfunction occurs as a side effect, compounds that suppress the side effect can be similarly screened.

  The screening method according to the present invention is cost-effective in screening compounds because the test can be performed with a treadmill. Further, since this screening method is simple to implement and can be automated, the screening time can be shortened and various compounds can be screened in a short time.

  Hereinafter, although the embodiment described above will be specifically described with reference to examples, this is an example of implementation and the present invention is not limited to this example.

<Example 1: Motor function evaluation for a brain contusion model mouse>
=== Preparation of a brain contusion model mouse ===
Six week old BALB / c strain female mice and six week old C57B1 / 6 strain female mice were used in this study. These mice were bred in cages where the light-dark cycle of lighting was 7:00 to 19:00 and food or water could be freely consumed.

To create a brain contusion model mouse, the mouse head was fixed with a stereotaxic device for small animals under 10% Nembutal anesthesia, and the scalp was incised 1.5 cm in the direction of the scalp and tail, and then a dental drill was used. The skull corresponding to the left frontal cortex (motor cortex site) was thinly removed to a diameter of 2.5 mm. Next, using a cryosurgical device Amoys Cryo ACU22-XT (Keeler and Winer Co., Ltd.) and a retinal detachment probe (standard P-2355, diameter 2.5 mm) (Keyler and Winer Co., Ltd.) connected with a CO ₂ cylinder, A brain contusion with a diameter of 2.5 mm was prepared by applying the tip of the probe set at −80 ° C. to the skull after removing the skull at intervals of 30 seconds × 5 times (cry group). As a control, mice that had only skin incision in the head and were not subjected to cryosurgery were also produced (sham group).

  In the cryo group, as shown in Fig. 3, the cerebral cortex motor area has 1 contusion site (cerebral cortex motor area partial damage), 2 places (cerebral cortex motor area partial damage) and 4 places (cerebral cortex). (Motor field all-injury) mice were prepared and referred to as 1-site model, 2-location model, and 4-location model, respectively.

  In addition, the brain contusion was confirmed by performing HE staining with respect to the brain section.

=== Slipping test and rotarod treadmill test ===
The “Slipping test” using the motor function evaluation method of the present invention was performed on the model mouse produced as described above. In this test, a Rotarod treadmill (Muromachi) with a constant rotation speed (5 to 6 rpm) was used. On the day before this test, in order to obtain accurate test results, the mice were subjected to walking training for 5 minutes using the same rotarod treadmill as in this test. In this test, first, it was confirmed that the mouse was able to get on the surface of the rotary shaft of the rotarod treadmill, and then the mouse walk on the surface of the rotary shaft was observed, and normal walking was possible. The number of times the foot was slid without counting was counted for 1 minute.

  As a control test, a “rotor rod treadmill test”, which is a conventional motor function evaluation method, was performed. As in the Slipping test, in order to obtain accurate test results, the mice were trained for 5 minutes on the day before the test using the same rotarod treadmill as in the test. In this test, first, the mouse was placed on the surface of the rotary shaft of the rotarod treadmill whose rotational speed was maintained at 2 rpm, and after confirming that the mouse was on the surface of the rotational shaft, the rotational speed was 2 to 20 rpm. The speed was set to 2 rpm / 20 seconds, or the rotation speed was set to 4 to 40 rpm, the speed was set to 4 rpm / 20 seconds, and the time until the mouse dropped from the rotating shaft (maximum 600 seconds) was measured.

=== Evaluation of motor function in one place model ===
As described above, a brain contusion model mouse 1 model was prepared (30 seconds x 5 times x 1 location, interval 30 seconds), and a Slipping test and a rotarod treadmill test were performed (N = 5, * <0.05, ** p <0.01, *** p <0.005, **** p <0.001). The results of the Slipping test are shown in FIG. 4A, and the results of the rotarod treadmill test are shown in FIG. 4B.

  As for the results of the Slipping test, a significant difference was observed between the sham group and the cryo group until the 14th day of the brain contusion, whereas the results of the Rotarod treadmill test showed that the 2nd day of the brain contusion Only a significant difference was observed between the sham group and the cryo group. The reason why the Slipping test showed a difference in score over a longer period than the Rotarod treadmill test is considered to be because the Slipping test can detect a finer difference in motor function. Thus, it has become clear that the slipping test can measure motor function with higher sensitivity than the conventional motor function measurement method.

=== Evaluation of motor function in two places model ===
Similarly, two brain contusion model mice were prepared (30 seconds x 5 times x 2 places, interval 30 seconds), and a Slipping test and rotarod treadmill test were performed (N = 5, * <0.05, ** p <0.01, *** p <0.005). The results of the Slipping test are shown in FIG. 5A, and the results of the rotarod treadmill test are shown in FIG. 5B.

  As a result, in the Slipping test and the Rotarod treadmill test, a significant difference was observed between the sham group and the cryo group even on the 56th day of the brain contusion. In the case of the two-site model, the motor function impairment was larger than that in the one-site model, and it was considered that there was still a disorder that could detect the disorder sufficiently even on the 56th day of the brain contusion and the conventional motor function evaluation method.

=== Evaluation of motor function in 4 models ===
As shown below, two types of mice were used, and three types of four-point models were created by changing the usage of the cryosurgical device Amoyles Cryo ACU22-XT and the retinal detachment probe.
(1) C57Bl / 6 female mouse 30 seconds x 10 times x 4 places
(2) BALB / c female mouse 30 seconds x 10 times x 4 places
(3) BALB / c female mouse 30 seconds x 5 times x 4 places
The results of the Slipping test are shown in FIG. 6A, and the results of the rotarod treadmill test are shown in FIG. 6B (N = 5), * <0.05, ** p <0.01, *** p <0.005, **** p < 0.001).

  As a result, in the Slipping test, a significant difference in motor function was observed between the sham group and the Cryo group until day 56 of brain contusion in both strains of mice. On the other hand, in the rotarod treadmill test, only a significant difference in motor function was observed between the sham group and the cryo group in only the C57B1 / 6 mouse, while in the BALB / c mouse, the sham group There was no significant difference between the group and Cryo group. Thus, the slipping test was able to detect motor dysfunction even in mouse strains that could not be detected by the conventional motor function measurement method. Therefore, it was also found here that the slipping test can measure motor function with higher sensitivity than the rotarod treadmill test.

<Example 2: Motor function evaluation after drug administration to brain contusion model mice>
=== Administration of drug to brain contusion model mouse ===
In the same manner as in Example 1, two models of brain contusion model mice were prepared (30 seconds × 5 times × 2 locations, interval 30 seconds), and the following experiments were performed using the brain contusion model mice.

  For brain contusion model mice, prepare 5 μl of physiological saline (0.9% NaCl) in the control group and 5 μl of mouse IL-12 (4 ng / μl) in the IL-12 administration group in the Ito microsyringe (MS-N05). Then, the syringe was placed in a stereotaxic apparatus and immediately administered to the cerebral ventricle of a brain contusion model mouse. The position where the needle was injected was 1 mm to the left from the center of the Bregma, 0.5 mm to the rear, 2 mm in depth, and the injection speed was 5 μl / 5 minutes.

  After administration of physiological saline or IL-12, the scalp was closed using a medical clip, kept warm until anwakening from anesthesia, and returned to the home cage after awakening.

=== Motor function evaluation after drug administration to brain contusion model mice ===
Thus, the Slipping test and the Rotarod treadmill test were performed on the brain contusion model mice administered with IL-12 (control group N = 8, IL-12 administration group N = 9, * <0.05, ** p <0.01, *** p <0.005, **** p <0.001). The results of the Slipping test are shown in FIG. 7A, and the results of the rotarod treadmill test are shown in FIG. 7B.
As a result, both the Slipping test and the Rotarod treadmill test showed a tendency that the motor function was recovered in the IL-12 group as compared with the control group.

  In the Slipping test, a significant difference in motor function was observed between the IL-12 administration group and the control group until the 56th day of brain contusion. On the other hand, in the rotarod treadmill test, a significant difference in motor function was observed between the IL-12 administration group and the control group until the 28th day of brain contusion. There was no significant difference in motor function between the 12 administration group and the control group.

  Thus, it became clear that the slipping test is effective as a method for evaluating the effectiveness of therapeutic agents for motor dysfunction.

In one Example which concerns on this invention, it is a figure which shows a motor function evaluation apparatus, and this figure is a figure of a rotarod treadmill. In one Example which concerns on this invention, it is a figure which shows a motor function evaluation apparatus, This figure is an enlarged view which expanded the rotating shaft vicinity, when a rotarod treadmill is seen from the front. In one Example which concerns on this invention, it is the perspective view seen from the side of the motor function evaluation apparatus, and this figure is a figure which shows the motor function apparatus whose detection apparatus is an infrared sensor. In one Example which concerns on this invention, it is the perspective view seen from the side of the motor function evaluation apparatus, and this figure is a figure which shows the motor function apparatus whose detection apparatus is a moving image camera. In one Example which concerns on this invention, it is a figure showing the produced brain contusion model mice (1 place, 2 places, 4 places). In one Example which concerns on this invention, it is a graph showing the result of the behavioral experiment in a brain contusion model mouse 1 place model, and this figure represents the Slipping test. In one Example which concerns on this invention, it is a graph showing the result of the behavioral experiment in a brain contusion model mouse 1 place model, and this figure represents the rotarod treadmill test. In one Example which concerns on this invention, it is a graph showing the result of the behavioral experiment in a brain contusion model mouse 2 place model, and this figure represents the Slipping test. In one Example which concerns on this invention, it is a graph showing the result of the behavioral experiment in a brain contusion model mouse 2 place model, and this figure represents the rotarod treadmill test. In one Example which concerns on this invention, it is a graph showing the result of the behavioral experiment in a brain contusion model mouse 4 place model, This figure represents the Slipping test. In one Example which concerns on this invention, it is a graph showing the result of the behavioral experiment in a brain contusion model mouse 4 place model, and this figure represents the rotarod treadmill test. In one Example which concerns on this invention, it is a graph showing the result of the behavioral experiment after inject | pouring IL-12 in the ventricle in a two place model, This figure represents the Slipping test. In one Example which concerns on this invention, it is a graph showing the result of the behavioral experiment after inject | pouring IL-12 in the ventricle in a two place model, This figure represents the rotarod treadmill test.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Treadmill 2 Infrared 3 Infrared transmitter 4 Mouse foot 5 Measuring device 6 Rotating shaft 7 Movie camera 8 Measuring device

Claims (12)

A method for evaluating motor dysfunction in vertebrates other than humans,
A method of measuring the number of times a subject slides on a treadmill without being able to normally walk or run normally.   The method according to claim 1, wherein the motor dysfunction is a disorder caused by a neurological disease.   The method according to claim 1, wherein the treadmill is a rotarod treadmill. A method for diagnosing diseases associated with motor dysfunction in vertebrates other than humans,
A method of measuring the number of times a subject slides on a treadmill without being able to normally walk or run normally. A method for evaluating treatment for a motor dysfunction in a non-human vertebrate having a motor dysfunction,
A method of measuring the number of times a subject slides on a treadmill without being able to normally walk or run normally. A method for evaluating the effectiveness of a therapeutic agent for a motor dysfunction for a non-human vertebrate having a motor dysfunction,
A method of measuring the number of times a subject slides on a treadmill without being able to normally walk or run normally. A safety evaluation method for evaluating the safety of a drug when administering a drug capable of developing motor dysfunction as an adverse event to a non-human vertebrate,
A safety evaluation method characterized in that the degree of the motor dysfunction is evaluated by measuring the number of times the subject slides on the treadmill without normal walking or normal running. A motor function evaluation apparatus for evaluating a vertebrate motor function,
With treadmill,
A monitoring device for monitoring the walking or running of the subject on the treadmill;
A measuring device for measuring the number of times the subject slides on the treadmill without being able to normally walk or run normally; and
Motor function evaluation device with   The motor function evaluation apparatus according to claim 8, wherein the monitoring apparatus includes a detection device for detecting that the subject slides a foot.   The motor function evaluation apparatus according to claim 9, wherein the detection device includes an infrared sensor.   The motor function evaluation device according to claim 9, wherein the detection device includes a video camera. A method for screening an effective therapeutic agent for the motor dysfunction using the therapeutic agent efficacy evaluation method according to claim 6.

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