Construction method and application of animal epilepsy model

Abstract

The invention relates to the technical field of medical experimental animal models, in particular to a construction method and application of an animal epilepsy model. The construction method of the animal epilepsy model provided by the invention comprises the following steps: performing anesthesia treatment on a mouse; tranexamic acid is injected into the side ventricle of the anesthetized mouse in a brain stereotactic administration mode; and recording and evaluating the epileptic seizure grade of the mouse injected with the tranexamic acid by adopting a Racine grading standard. The animal epilepsy model constructed by the invention is high in epilepsy causing rate, simple in modeling process, easy to operate and repeat, and capable of better reflecting epilepsy caused by tranexamic acid, so that the animal epilepsy model can be used for researching tranexamic acid related epilepsy pathogenesis and targeted intervention measures.

Description

Technical Field

[0001] The present application belongs to the technical field of medical experimental animal models, and in particular, relates to a method for constructing an animal epilepsy model and its application. Background Art

[0002] As an antifibrinolytic drug, tranexamic acid has become an important component of the IA-level perioperative blood protection recommended by various guidelines because it can reduce the risk of perioperative blood loss and the need for blood transfusion without increasing the risk of thrombosis. It is widely used in multiple clinical scenarios such as cardiovascular surgery, obstetric surgery, transplant surgery, and trauma surgery. With the widespread use of tranexamic acid, its specific neurological complication, epilepsy, has gradually attracted the attention of medical workers. In cardiovascular surgery, tranexamic acid-related epilepsy often occurs 5 to 8 hours after surgery (that is, when the effect of anesthetic drugs disappears and the patient's consciousness becomes clear). The overall incidence reported in previous studies is 0.3% to 11%, and it is dose-dependent and positively correlated. The discovery and diagnosis of this type of epilepsy mainly depends on the observation of epilepsy-like symptoms such as local myoclonus and generalized tonic-clonic by medical staff, so its actual incidence may be higher. Although sedatives can partially treat symptoms, some patients may relapse 24 to 48 hours after surgery. This type of epilepsy can lead to a longer ICU stay and total hospital stay, and may also increase the risk of postoperative neurological complications (defined as delirium and / or stroke) and death. Therefore, tranexamic acid-related epilepsy has an adverse effect on the patient's early recovery, increasing the difficulty of medical care and the economic burden on the family and society.

[0003] Animal epilepsy models are one of the important means to study the pathogenesis and treatment of epilepsy. Currently, common animal epilepsy models include epilepsy models induced by chemical epileptogens, epilepsy models ignited by electrical stimulation of sensitive parts of the brain, gene knockout and transgenic animal epilepsy models, etc. For example, after anesthetizing rats, laminectomy is performed to directly expose the spinal cord, fibrin adhesive or collagen sponge soaked with tranexamic acid is directly covered on the spinal cord segments, and the neuroexcitatory effect of tranexamic acid is evaluated by detecting animal pain perception and hind limb excitatory movements. Or after anesthetizing rats, craniotomy is performed to expose the cerebral cortex, fibrin adhesive soaked with tranexamic acid is directly applied to the cerebral cortex, and the changes in the animal's electroencephalogram are directly detected through electrodes on the surface of the skull, and the excitatory movement of the hind limbs is detected to evaluate the neuroexcitatory effect of tranexamic acid. However, the modeling process of these methods is complicated, and the detection of EEG activity is mostly carried out under strictly controlled conditions, which limits the natural behavior of animals and fails to fully explore the correlation between EEG changes and behavioral performance; and there are still certain differences between the neural excitability revealed by behavioral studies and the epileptic activity shown by the electroencephalogram, and the two are not completely equivalent. In addition, there are reports of recording animal behavior and EEG changes after intravenous injection of large doses of tranexamic acid in rats or cats. However, it is difficult to exclude the possibility that epilepsy induced by intravenous injection of tranexamic acid is caused by non-neural excitatory effects such as cerebral thrombosis and drug toxicity. Therefore, the existing animal models are difficult to accurately reflect the epilepsy actually caused by tranexamic acid. Summary of the invention

[0004] The purpose of this application is to provide a method for constructing an animal epilepsy model and its application, aiming to solve how to better construct an animal model of tranexamic acid-induced epilepsy.

[0005] In order to achieve the above application purpose, the technical solution adopted in this application is as follows:

[0006] In a first aspect, the present application provides a method for constructing an animal epilepsy model, comprising:

[0007] The mice were anesthetized;

[0008] Injecting tranexamic acid into the lateral ventricle of the anesthetized mouse by stereotaxic administration;

[0009] The Racine grading system was used to record and evaluate the epileptic seizure grade of the mice after the injection of tranexamic acid.

[0010] In the second aspect, the present application provides an application, namely, the application of the animal epilepsy model obtained by the above-mentioned construction method of the present application in the study of the pathogenesis and treatment of tranexamic acid-related epilepsy.

[0011] In the method for constructing an animal epilepsy model provided in the first aspect of the present application, tranexamic acid is injected into the lateral ventricle of a rodent mouse by stereotaxic administration, and then the Racine grading standard is used to record and evaluate the epileptic seizure grade of the mouse after the injection of tranexamic acid, so that an animal epilepsy model caused by tranexamic acid can be accurately constructed. The animal epilepsy model constructed in the present application has a high epilepsy rate, and the modeling process is simple, easy to operate and easy to repeat, which can better reflect the epilepsy caused by tranexamic acid, and therefore can be used for the study of the pathogenesis of tranexamic acid-related epilepsy and targeted intervention measures.

[0012] The application provided in the second aspect of the present application is based on the advantages of the animal epilepsy model constructed by the construction method of the first aspect of the present application, so that it can be better used for the study of the pathogenesis and treatment of tranexamic acid-related epilepsy. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0014] Figure 1 It is the behavioral evaluation result of epilepsy induced by tranexamic acid in the method for constructing an animal epilepsy model provided in the examples of the present application; the seizure situation of each mouse within 6 hours after administration of the control group (n=6) and the experimental group (n=6), the horizontal axis is time (seconds), and the vertical axis is Racine grade;

[0015] Figure 2 It is the electroencephalogram evaluation and verification of tranexamic acid-induced epilepsy in the method for constructing an animal epilepsy model provided in the embodiment of the present application; A is the baseline electroencephalogram, B is the paroxysmal slow wave and the corresponding behavioral manifestation, C is the paroxysmal spike wave and the corresponding behavioral manifestation, D is the spike-slow complex wave and the corresponding behavioral manifestation, E is the paroxysmal spike wave and the corresponding behavioral manifestation, and F is the continuous polyspike wave and the corresponding behavioral manifestation. DETAILED DESCRIPTION

[0016] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present application more clearly understood, the present application is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and are not used to limit the present application.

[0017] In this application, the term "and / or" describes the association relationship of associated objects, indicating that there may be three relationships. For example, A and / or B can mean: A exists alone, A and B exist at the same time, and B exists alone. A and B can be singular or plural. The character " / " generally indicates that the associated objects are in an "or" relationship.

[0018] In the present application, "at least one" means one or more, "more than one" means two or more. "At least one of the following" or similar expressions refers to any combination of these items, including any combination of single or plural items.

[0019] It should be understood that in the various embodiments of the present application, the size of the serial numbers of the above-mentioned processes does not mean the order of execution, some or all of the steps can be executed in parallel or sequentially, and the execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0020] The terms used in the embodiments of the present application are only for the purpose of describing specific embodiments, and are not intended to limit the present application. The singular forms "a", "said" and "the" used in the embodiments of the present application and the appended claims are also intended to include plural forms, unless the context clearly indicates other meanings.

[0021] The weight of the relevant components mentioned in the embodiment description of the present application can not only refer to the specific content of each component, but also represent the proportional relationship between the weights of the components. Therefore, as long as the content of the relevant components is proportionally enlarged or reduced according to the embodiment description of the present application, it is within the scope disclosed in the embodiment description of the present application. Specifically, the mass described in the embodiment description of the present application can be a mass unit known in the chemical industry such as μg, mg, g, kg, etc.

[0022] The terms "first" and "second" are used only for descriptive purposes to distinguish objects such as substances from each other, and should not be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features. For example, without departing from the scope of the embodiments of the present application, the first XX may also be referred to as the second XX, and similarly, the second XX may also be referred to as the first XX. Thus, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features.

[0023] Tranexamic acid, also known as tranexamic acid, tranexamic acid, and hemostatic acid, has a chemical name of trans-4-aminomethylcyclohexanecarboxylic acid: it is an antifibrinolytic drug, and its mechanism is to inhibit the conversion of plasminogen into plasmin by binding to plasminogen, thereby inhibiting fibrinolysis and reducing bleeding. Due to its definite hemostatic effect, it is widely used to prevent and treat bleeding caused by physiological or pathological factors such as surgery, trauma, and menorrhagia.

[0024] Bregma is an anatomical landmark located at the junction of the frontal and parietal bones, where the coronal and sagittal sutures intersect. Bregma is often used as a reference point to identify specific areas of the brain in rodents during stereotaxic experiments (such as intraventricular injections or electrode implantation).

[0025] Stereotactic technique: a technique for accurately injecting drugs into specific areas of the brain. This method uses a stereotaxic instrument and a standardized brain coordinate system to accurately locate anatomical landmarks and then inject drugs or other substances (such as viral vectors, probes, etc.) into the predetermined brain area.

[0026] Mechanistic studies of animal epilepsy models can not only reveal the various pathophysiological bases of epilepsy, but also promote the development of related targeted therapies. It can also serve as a cornerstone for evaluating the efficacy and safety of new drugs, and also provide an important basis for studying the comorbidity between epilepsy and other neurological diseases. Therefore, establishing an animal epilepsy model induced by tranexamic acid is crucial for a deeper understanding of its mechanism and the development of specific new treatment strategies.

[0027] In cardiac surgery, due to the large demand for tranexamic acid and the possible destruction of the blood-brain barrier by systemic inflammatory response, a large amount of tranexamic acid enters the central nervous system, thereby inducing epileptic seizures. In animal modeling, compared to peripheral route administration, stereotaxic ventricular administration is a mature basic experimental technology with the advantages of accurate positioning, small dosage and relatively low mortality. Based on this, the present application embodiment adopts brain stereotaxic administration to inject tranexamic acid into the lateral ventricle of mice to construct an epilepsy animal model caused by tranexamic acid, and the specific scheme is as follows.

[0028] In a first aspect, an embodiment of the present application provides a method for constructing an animal epilepsy model. The construction method of the embodiment of the present application includes:

[0029] S01: Anesthetize the mouse;

[0030] S02: Using stereotaxic administration, tranexamic acid was injected into the lateral ventricle of anesthetized mice;

[0031] S03: The Racine grading system was used to record and evaluate the epileptic seizure grade of mice after injection of tranexamic acid.

[0032] The animal epilepsy model constructed in the embodiment of the present application has a high epilepsy rate, and the modeling process is simple, easy to operate and repeat, and can better reflect the epilepsy caused by tranexamic acid. Therefore, it can be used for the study of the pathogenesis of tranexamic acid-related epilepsy and targeted intervention measures.

[0033] In some embodiments, the mouse provided in step S01 can be a C57BL / 6J mouse, for example, a 6-8 week old male C57BL / 6J mouse. In the establishment of animal epilepsy models, rodents are often used because of their genetic stability, easy reproduction, low experimental cost, and convenience for subsequent genetic modification. In this embodiment of the application, C57BL / 6J mice are used for modeling.

[0034] In some embodiments, the anesthesia treatment in step S01 may be to anesthetize the mouse using isoflurane. Specifically, the mouse is anesthetized using isoflurane, which contains 3-5% oxygen.

[0035] In some embodiments, the coordinates of the lateral ventricle of the mouse injected with tranexamic acid after anesthesia in step S02 are: 0.4-0.6 mm posterior to the coronal sagittal point, ±(0.8-1.2) mm lateral to the coronal sagittal point, and 1.8-2.2 mm ventral to the coronal sagittal point. Further, the coordinates of the lateral ventricle of the mouse are: 0.5 mm posterior to the coronal sagittal point, ±1.0 mm lateral to the coronal sagittal point, and 2.0 mm ventral to the coronal sagittal point.

[0036] In some embodiments, in the step of injecting tranexamic acid into the lateral ventricle of anesthetized mice, the amount of tranexamic acid injected into each mouse is 14 to 16 μg. For example, it can be 15 μg. Due to the accurate administration of tranexamic acid into the ventricle under stereotaxic location, tranexamic acid induces epileptic behavior and significant EEG at the threshold dose, the dose required for modeling is small, the operation is convenient and simple, and the phenotype is accurate, which is convenient for subsequent mechanism exploration and development of intervention measures.

[0037] Further, the concentration of tranexamic acid in the injection is 7 to 8 μg / μl. For example, 2 μl of injection (tranexamic acid concentration is 7.5 μg / μl) can be injected. Wherein physiological saline is used as a solvent, i.e., a sodium chloride aqueous solution with a mass percentage of 0.9%. The embodiment of the present application determines the optimal concentration and dosage of tranexamic acid that induces strong epileptic phenotype attacks with low mortality through basic experiments and early explorations, and thus can be expanded to other animals according to data such as the surface-to-body ratio. Establishment of the intraventricular administration model of tranexamic acid.

[0038] The present application example is based on the peak concentration of tranexamic acid in the cerebrospinal fluid of patients undergoing open thoracoabdominal aorta surgery, and the gradient concentration set in previous animal experiments, and tranexamic acid is directly injected into the lateral ventricle of C57BL / 6J mice using stereotaxic technology. Subsequently, the Racine scoring standard is used to record the behavioral changes of mice after administration, and indicators such as the rate and duration of generalized epileptic seizures are calculated to screen out a dose with significant phenotype and low mortality, which is used as the threshold dose for subsequent in vivo EEG analysis verification.

[0039] In some embodiments, the Racine grading standard in step S03 includes: Grade O: no response. Grade I: head and face twitching, chewing; Grade II: rhythmic nodding or whole body startling; Grade III: unilateral forelimb clonus; Grade IV: whole body clonic convulsion with hind limb standing, often accompanied by bilateral forelimb clonus; Grade V: standing with falling or whole body tonic-clonic seizure. Specifically, according to the Racine grading standard, the behavioral changes of mice within 5 to 6 hours after the injection of tranexamic acid can be recorded.

[0040] In some embodiments, the method further comprises: performing epilepsy verification according to the electroencephalogram (EEG) of mice. The epilepsy verification of the above-constructed model is verified by performing EEG on another independent mouse. In the epilepsy verification, the drug tranexamic acid is also injected into the lateral ventricle of the mouse, and the coordinate position of the injected lateral ventricle and the dosage of tranexamic acid are the same as the aforementioned construction method, except that another device is required to obtain the EEG.

[0041] In some embodiments, the steps of epilepsy verification include: performing an operation of implanting electrodes on the skull and a lateral ventricle drug delivery catheter on another mouse under anesthesia, and then connecting the electrodes on the skull of the mouse that has recovered after the operation to an electroencephalogram component, injecting tranexamic acid through the lateral ventricle drug delivery catheter after recording the baseline EEG, and then recording the mouse's electroencephalogram and synchronous behavioral changes.

[0042] The coordinates of the electrodes on the skull can be: ML (x-axis): ±2.75 mm, AP (y-axis): -0.8 mm, -3.2 mm. The coordinates of the catheter implanted in the lateral ventricle are: 0.4-0.6 mm posterior to the coronal sagittal point, ±(0.8-1.2) mm lateral to the sagittal point, and 1.8-2.2 mm ventral to the sagittal point.

[0043] In some embodiments, in the step of recording the EEG and synchronous behavioral changes of mice, the changes are continuously recorded within 2 to 2.5 hours after administration.

[0044] In some embodiments, in the step of recording the EEG and synchronous behavioral changes of mice, a 3-second search window and a 3-second sliding window are used, and an automatic power search method with a threshold set to 10000 μV2 / Hz is applied to all recorded EEG signal channels.

[0045] In the second aspect, the present application provides an application. The application of the present application is the application of the animal epilepsy model obtained by the construction method provided in the first aspect of the present application in the study of the pathogenesis and treatment of tranexamic acid-related epilepsy.

[0046] The animal epilepsy model constructed in the embodiment of the present application is to directly administer tranexamic acid into the lateral ventricle under the guidance of brain stereotactic administration to model epilepsy. Compared with the previous in vivo animal model of tranexamic acid, the effect of anesthetic drugs on epilepsy evaluation is reduced, the operation is simple, and the tranexamic acid drug exerts a definite neuroexcitatory effect, has a high epileptogenic rate, strong repeatability, and good accuracy. Such an animal epilepsy model is convenient for the exploration of tranexamic acid-related epilepsy mechanisms and specific intervention or treatment research.

[0047] The following describes the invention in conjunction with specific embodiments.

[0048] Example

[0049] 1. Experimental equipment

[0050] Experimental animals: 6-8 week old male C57BL / 6J mice (Beijing Weitonglihua Experimental Animal Technology Co., Ltd.); tranexamic acid (purity 99%, Xi'an Jinheng Chemical Co., Ltd.); anesthetic drugs: isoflurane (R510-22-10, Shenzhen Ruiwode Life Science Technology Co., Ltd.); experimental instruments: mouse gas anesthesia machine (R500, Shenzhen Ruiwode Life Science Technology Co., Ltd.), brain stereopotential injection device (68804, Shenzhen Ruiwode Life Science Technology Co., Ltd.), 10μL Hamilton microsyringe, camera (Liantu S9), six-channel head electrode (KD-EEG / EMG-PCB, Kedou (Suzhou) Brain-Computer Technology Co., Ltd.), Sirenia Seizure Pro (v.1.7.9, Pinnacle Technology).

[0051] 2. Methods for constructing animal epilepsy models

[0052] Twelve 6-8 week old C57BL / 6J male mice were bred in an environment with controlled temperature (21-25°C) and light (12 hours on / 12 hours off) and provided with free access to food and water one week before the experiment. All mice were anesthetized with isoflurane (3-5% oxygen) 5 minutes before the start of the stereotaxic brain injection. After the anesthesia, the mice were placed in a stereotaxic apparatus and injected with 2 μl of injection solution (containing 7.5 μg / μl tranexamic acid, saline as a solvent) or saline into the lateral ventricle (lateral ventricle coordinates: from bregma point: 0.5 mm posterior; ±1.0 mm lateral; 2.0 mm ventral), and the injection was stopped for 3 minutes to prevent reflux. After the injection, the mice were returned to the cage and observed for 6 hours in real time. Among them, 6 mice injected with injection solution containing tranexamic acid were the experimental group (n=6), and the other 6 mice injected with saline were the control group (n=6).

[0053] The Racine standard was used to record and evaluate the seizure grade of epilepsy (Racine standard - Grade I: head and face twitching, chewing; Grade II: rhythmic nodding or whole body startle; Grade III: unilateral forelimb clonus; Grade IV: whole body clonic convulsion with hind limb standing, often accompanied by bilateral forelimb clonus; Grade V: standing with falling or whole body tonic-clonic seizure). Among them, grade I-III seizures were regarded as partial paroxysmal epilepsy, and grade IV-V seizures were regarded as generalized epilepsy. The rate, latency and duration of generalized epilepsy and mortality of epileptic seizures were recorded.

[0054] The results are as follows Figure 1 As shown: In the control group, mice occasionally showed abnormal behaviors such as behavioral cessation or short nodding after drug administration (Racine I-II grade). In the experimental group, mice developed generalized epileptic seizures within a few minutes after drug administration. During the process, the animals had difficulty maintaining the righting reflex, which manifested as rhythmic limb clonus and (or) opisthotonos after lying down on one side of the limb, synchronous flapping of the bilateral forelimbs when standing, running and (or) jumping, etc. Over time, these generalized seizures can be alleviated into localized epileptic seizures such as unilateral limb myoclonus and rhythmic nodding. Among them, the incidence of generalized epilepsy in the experimental group was higher than that in the control group (0 / 6vs4 / 6, Fisher's exact probability method p=0.06), and no deaths were observed between the two groups. In addition, the duration of generalized epilepsy in the experimental group was significantly longer than that in the control group (KW rank sum test p=0.02).

[0055] 3. EEG epilepsy verification

[0056] Thirteen 6-8-week-old C57BL / 6J male mice were randomly divided into two groups for EEG verification. Before EEG observation, the experimental group (n=8, injected with tranexamic acid-containing injection) and the control group (n=5, injected with normal saline) each underwent deep electrode and lateral ventricle drug delivery catheter implantation surgery. The entire surgical procedure was anesthetized with isoflurane (containing 3-5% oxygen). The mice were placed in a stereotaxic device. After exposing the skull, electrodes were implanted at the following coordinates: ML (x-axis): ±2.75mm, AP (y-axis): -0.8mm, -3.2mm. A skull drill was used to drill a hole on the outside of the left ventricle and an acrylic injection cannula was inserted as a drug delivery catheter for subsequent drug delivery. After the operation was completed, the electrode and the drug delivery catheter were fixed with dental cement. After 7 days of recovery after the operation, the mice were placed in a transparent cage alone, and the EEG assembly was fixed to the electrode on the mouse skull with screws. The preamplifier was connected to the electrode and connected to the multi-channel commutator. An infrared LED camera was used to capture simultaneous video recording synchronized with the EEG recording. After recording the baseline EEG, the experimental group received an intracerebroventricular injection of 2 μl of an injection solution (containing 7.5 μg / μl tranexamic acid and saline as a solvent) through the drug delivery catheter, while the control group received saline. The EEG and synchronous behavioral changes of the mice were continuously recorded for 2 hours after administration, and the EEG was automatically identified by Sirenia Seizure Pro. Epileptic seizures were defined as rhythmic or repetitive tracings lasting more than 10 seconds with an amplitude up to 3 times the baseline. An automatic power search method with a threshold set to 10,000 μV2 / Hz was applied to all recorded EEG signal channels using a 3-second search window and a 3-second sliding window. Finally, all identified epileptic events were manually verified using EEG and video.

[0057] The results are as follows Figure 2 As shown in the figure: No obvious epileptic-like changes were observed in the behavior and EEG of the 5 mice in the control group. Among the 8 mice in the experimental group, 5 were observed to have abnormal EEG epileptic-like discharge signals; one of them only showed behavioral cessation and staring attacks, while the EEG showed intermittent spikes and sharp waves and spontaneously returned to normal; 4 animals had typical generalized tonic-clonic seizures and epileptic-like EEG discharges, and the animals' convulsions and clonus could be synchronized with epileptic waves, and the waveforms were mostly scattered or continuous spikes, sharp waves, and slow waves alternately. During the discharge process, most animals found it difficult to maintain the righting reflex. After about 1.5-2 hours, 2 animals no longer had widespread seizures, and the EEG waves became basic waves. The other 2 animals had more severe clonic behaviors such as running, jumping, and falling as the widespread epileptic seizures progressed, and the EEG also changed to continuous spikes and multiple spikes with gradually increasing frequency and amplitude. Subsequently, the animals stopped breathing and heartbeat, and the EEG gradually became flat.

[0058] In summary, the tranexamic acid acute epilepsy model of rodent C57BL / 6J mice established in the examples of the present application (2 μl of tranexamic acid with a concentration of 7.5 μg / μl was injected into the lateral ventricle of 6-8 week male C57BL / 6J mice under stereotaxic positioning), and evaluated from the aspects of behavior and electrophysiology. The results show that the animal epilepsy model constructed in the examples of the present application has a high epilepsy rate, which can be manifested as local myoclonus and generalized tonic-clonic seizures. The modeling process is simple, easy to operate and easy to repeat, and can be used for the study of the pathogenesis of tranexamic acid-related epilepsy and targeted intervention measures.

[0059] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims

1. A method for constructing an animal epilepsy model, characterized in that: include: The mice were anesthetized; Injecting tranexamic acid into the lateral ventricle of the anesthetized mouse by stereotaxic administration; The Racine grading system was used to record and evaluate the epileptic seizure grade of the mice after the injection of tranexamic acid.

2. The construction method according to claim 1, characterized in that: In the step of injecting tranexamic acid into the lateral ventricle of the anesthetized mouse, the coordinates of the lateral ventricle of the mouse are: 0.4-0.6 mm posterior to the coronal sagittal point, ±(0.8-1.2) mm lateral to the coronal sagittal point, and 1.8-2.2 mm ventral to the coronal sagittal point.

3. The construction method according to claim 2, characterized in that: The coordinates of the mouse lateral ventricle are: 0.5 mm posterior to the coronal sagittal point, ±1.0 mm lateral to the point, and 2.0 mm ventral to the point.

4. The construction method according to claim 1, characterized in that: In the step of injecting tranexamic acid into the lateral ventricle of the anesthetized mouse, the injection amount of tranexamic acid per mouse is 14-16 μg.

5. The construction method according to claim 4, characterized in that: The tranexamic acid is injected in the form of an injection, and the concentration of tranexamic acid in the injection is 7-8 μg / μl.

6. The construction method according to claim 1, characterized in that: In the step of recording and evaluating the epileptic seizure grade of mice after injection of tranexamic acid using the Racine grading standard, the behavioral changes of mice within 5 to 6 hours after injection of tranexamic acid are recorded.

7. The construction method according to any one of claims 1 to 6, characterized in that: Also includes: Epilepsy verification was performed based on the EEG of mice.

8. The construction method according to claim 7, characterized in that: The steps of epilepsy verification include: using another mouse to perform a skull electrode and lateral ventricle drug delivery catheter implantation surgery under anesthesia, then connecting the skull electrodes of the mouse that has recovered after the operation to an electroencephalogram component, injecting tranexamic acid through the lateral ventricle drug delivery catheter after recording the baseline EEG, and then recording the mouse's electroencephalogram and synchronous behavioral changes.

9. The construction method according to claim 8, characterized in that: In the step of recording the electroencephalogram and synchronous behavioral changes of the mouse, the changes within 2 to 2.5 hours after administration are continuously recorded; and / or, In the step of recording the EEG and synchronous behavioral changes of mice, a 3-second search window and a 3-second sliding window are used, and an automatic power search method with a threshold set to 10000 μV2 / Hz is applied to all recorded EEG signal channels.

10. Application of the animal epilepsy model obtained by the construction method according to any one of claims 1 to 9 in the study of the pathogenesis and treatment of tranexamic acid-related epilepsy.

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