A method for constructing a mouse acute epilepsy model

Abstract

The present application aims to develop an animal model which can focus on the classic symptoms of epilepsy and can well evaluate the drug efficacy of epilepsy. The mouse acute epilepsy model constructed in the present application shows a high success rate and stability in inducing classic symptoms of epilepsy (neuronal injury, hippocampal sclerosis, glial cell proliferation, generalized tonic-clonic seizures, etc.), as well as anxiety, depression and cognitive impairment and other symptoms accompanying epilepsy. In the construction method of the mouse acute epilepsy model of the present application, 6-hydroxydopamine is injected intravenously, IL-1beta is injected intraperitoneally, and glycine+ultraviolet light stimulation+ultrasonic treatment+starvation treatment and acetic acid fumigation are used to induce the mouse acute epilepsy model. This multi-factor induced acute epilepsy animal model is consistent with the etiology that epilepsy is induced by multiple factors, and can better simulate the characteristics of human epilepsy.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of construction of animal models of children's diseases, and particularly relates to a method for constructing a mouse acute epilepsy model. BACKGROUND

[0002] Neonatal epilepsy is a common and frequently-occurring disease in clinic, and its pathogenesis is very complex, which has genetic factors and environmental factors. The childhood is a high-incidence stage of epilepsy, and long-term and repeated seizures can cause brain damage such as neuron damage, hippocampal sclerosis and glial cell proliferation, and cause long-term cognitive dysfunction. Epilepsy is a clinical syndrome caused by abnormal discharge of highly synchronized neurons in the brain, which has the clinical characteristics of seizure, transience, repetition and stereotypy. Epilepsy is a common nervous system disease, which is caused by highly synchronized activity of neurons in the brain, has complex etiology, suddenness, repeated attack and other characteristics, and the main treatment in clinic is long-term regular oral administration of antiepileptic drugs. Epilepsy is the second most stubborn disease of the nervous system, especially temporal lobe epilepsy, which seriously affects the work and life of human beings. Due to the difficulty of clinical research and the complexity of the pathogenesis, constructing an animal model is the most effective method, and an animal model of epilepsy is an essential tool for exploring the mechanism of epilepsy and screening antiepileptic drugs. Epilepsy is an episodic disease caused by various causes, and its pathogenesis is complex, and many mechanisms are still unknown. It is very important to establish an experimental animal model that can simulate human epilepsy for epilepsy research. Various animal models can be established by methods such as electrical stimulation and chemical drug induction, and different animal models have their corresponding advantages. In the experiment, appropriate selection should be made according to the experimental purpose.

[0003] Epilepsy is a central nervous system disease of brain dysfunction caused by abnormal synchronous discharges of neurons in the brain. Repeated seizures can also cause other co-morbidities such as depression, anxiety, dementia, migraine, heart disease, peptic ulcer and arthritis, etc. Temporal lobe epilepsy is the most common type of epilepsy. Even after standard treatment, about 30% of patients with epilepsy still show drug-resistant epilepsy, and are combined with anxiety, depression and cognitive impairment such as memory loss. The mechanism of epilepsy development may be related to neuronal loss, hippocampal mossy fiber sprouting, neurotransmitter imbalance and receptor function changes, glial cell proliferation, changes in aquaporin 4 expression, intestinal flora imbalance and neuroinflammation. Among them, neuronal loss may be one of the important pathological changes of refractory epilepsy, and hippocampal neuronal loss is also closely related to cognitive impairment and chronic recurrent seizures. However, we still do not understand the specific molecular mechanisms. Many current studies show that both apoptosis and autophagy pathways can be triggered by seizures, but the exact process of these phenomena in neuronal loss caused by epilepsy is still unclear. Therefore, exploring the molecular mechanisms of epilepsy development is still a problem to be solved. The pathophysiological mechanisms of seizures mainly involve inflammation, oxidative stress, autoimmunity, free radical damage, intracellular calcium overload, apoptosis, excitatory amino acid toxicity, cortical dysplasia, gene mutation, etc., involving changes at the molecular, cellular and neural network levels. These pathogenesis mechanisms produce a cascade effect and interact with each other, and then lead to secondary brain dysfunction.

[0004] Zhang et al. used 28-day-old rats to establish a variety of pediatric epilepsy models by intraperitoneal injection of pentylenetetrazole 32 mg / kg for 28 consecutive days. During the modeling process, as time increased, the convulsion grade of the rats gradually increased, from facial convulsions, staring, to generalized myoclonus, tonic-clonic convulsions, etc. The advantages of this modeling method are that it can simulate various pediatric epilepsy seizure forms, including primary epilepsy. The disadvantages are that the individual differences are large, and the animals are prone to death. Li et al. used 21-day-old rats to establish a model by intraperitoneal injection of 12 mg / kg kainic acid, and evaluated the convulsion degree of the rats using the rat epilepsy evaluation standard (0-V grade) developed by Racine. After 48 hours of kainic acid administration, the neurons of the epileptic rats were damaged (the color of the Nissl body was lighter, the morphology was disordered, and the number was reduced), and the number of apoptotic cells increased, suggesting that the epileptic rats had neuronal loss and brain damage. The advantages of this modeling method are that it can simulate the brain damage of human young children with epilepsy, and the disadvantages are that the individual differences are large, and the animals are prone to death. Barata et al. used 1-day-old piglets to establish a model by bilateral carotid artery ligation for 30 min and hypoxia, and used amplitude integrated electroencephalogram to detect the neurobehavior of seizure and neuromotor dysfunction. Wang et al. established a more severe juvenile epilepsy model by knocking out the Plppr5 gene of mice + hypoxia-ischemia, which showed that the mice lost the functions of exploration and memory. The study found that knocking out the Plppr5 gene could reduce the survival rate of HT22 cells, aggravate oxidative stress damage, reduce the proportion of survival mitochondria, and up-regulate the activity of mitochondrial autophagy. This model reveals the first direct link between Plppr5 gene knockout and neurobehavior and cognitive impairment after juvenile epilepsy seizure, and provides a potential mechanism explanation for the adverse consequences.

[0005] The main purpose of establishing an epilepsy animal model is to use the model to explore the causes and evolution of human epilepsy seizures, especially drug-resistant epilepsy seizures. In addition to the three common characteristics of chronicity, spontaneity, and recurrence, an ideal drug-resistant epilepsy animal model should also have the following characteristics: the seizure of the model should be the same as the clinical manifestations of human epilepsy. The current acute epilepsy model construction method still has the defects of unstable modeling, long cycle, low efficiency, and high animal mortality, and there is an urgent need for a simple and easy-to-control method for constructing an acute epilepsy model that is reliable, stable, has high modeling efficiency, and has low mortality. SUMMARY

[0006] The application aims to develop an animal model capable of focusing on the classic symptoms of epilepsy and capable of well performing the efficacy evaluation of epilepsy. The mouse acute epilepsy model constructed by the application shows a high success rate and stability in inducing classic symptoms of epilepsy (neuron damage, hippocampal sclerosis, glial cell proliferation, generalized tonic-clonic seizures, etc.), as well as anxiety, depression and cognitive impairment and other symptoms accompanying epilepsy. The research can well simulate the clinical onset of epilepsy, lay a good foundation for rapid screening of therapeutic drugs, and the modeling method is mature and reliable, short in cycle, low in cost, high in efficiency and low in animal mortality.

[0007] The application is realized by the following technical scheme:

[0008] A construction method of a mouse acute epilepsy model, characterized by comprising the following steps:

[0009] (1) Animal selection: select clean adult male C57BL / 6 mice with a weight of 18-22 g and an age of 8-10 weeks, and raise the mice in a mouse cage with 12 hours of light and 12 hours of darkness, free access to water and food, and an environmental temperature of 22-26 DEG C.

[0010] (2) Drug injection: after adaptive feeding of the experimental mice for two weeks, modeling is started; the mice are intravenously injected with 6-hydroxydopamine 03-1 mg / kg on the 1st, 5th and 15th days, and intraperitoneally injected with IL-1 beta 6-8 ug / kg and glycine 15-20 ug / kg on the 3rd, 8th and 20th days; IL-1 beta is injected first, and glycine is injected after 1 hour.

[0011] (3) Ultraviolet light stimulation: an ultraviolet lamp is arranged in the mouse cage, the ultraviolet lamp generates a wavelength of 280-320 nm, and the ultraviolet lamp is turned on for 10 minutes in the morning every day during the modeling period.

[0012] (4) Ultrasonic treatment: an ultrasonic generator is arranged in the mouse cage, the ultrasonic generator generates ultrasonic waves with a power of 1000 W and a frequency of 28-30 kHz, and the ultrasonic generator is turned on for 30 minutes in the afternoon every day.

[0013] (5), starvation treatment and acetic acid fumigation: after two weeks of modeling, the experimental mice are starved from the 15th day, and no food and water are provided to the mice, and the starvation treatment is performed once every other day for half a month, that is, on the 15th, 17th, 19th, 21st, 23rd, 25th, 27th and 29th days, the mice are starved, and on the 16th, 18th, 20th, 22nd, 24th, 26th and 28th days, the mice are normally fed. At the same time of the starvation treatment, acetic acid fumigation is performed (that is, on the 15th, 17th, 19th, 21st, 23rd, 25th, 27th and 29th days, acetic acid fumigation is performed), and the acetic acid fumigation is performed by pouring white vinegar and water into a steamer in a ratio of 1:1, and fumigation is performed twice a day, and each time fumigation is performed for 10 minutes. After 29 days of modeling, the mouse acute epilepsy model is obtained.

[0014] After 29 days of modeling, the model is evaluated through observation of the behavior of the mice, detection of cognition by the Morris water maze experiment, pathological observation, electroencephalogram recording, detection of the inflammation level by the ELISA method, observation of neuron cell apoptosis by TUNEL staining, and detection of the expression of P2X7 and NF-κB proteins in the hippocampal tissue by the Western blot method, and the results show that the mice exhibit typical symptoms of acute epilepsy, and the reliability and effectiveness of the acute epilepsy animal model are determined, that is, the causes of the disease, the symptoms, and the pathophysiology can be successfully obtained by the construction method of the present application.

[0015] The technical solution of the present application has the following advantages:

[0016] 1. In the construction method of the mouse acute epilepsy model of the present application, 6-hydroxydopamine is injected intravenously, IL-1β is injected intraperitoneally, and glycine + ultraviolet light stimulation + ultrasonic treatment + starvation treatment and acetic acid fumigation are performed to induce the mouse acute epilepsy model. This multi-factor induced acute epilepsy animal model is consistent with the view that epilepsy is induced by multiple factors in etiology, and can better simulate the characteristics of human epilepsy. The non-single-factor induced acute epilepsy animal model of the present application basically meets the three effectivenesses, whether from the perspective of pathophysiology theory or from the perspective of simulating typical clinical symptoms and treatment prediction, and is a relatively ideal animal model. The present application provides support for the multi-factor induced pathogenesis of epilepsy and provides a theoretical basis for the development of new solutions for the treatment of epilepsy.

[0017] 2. The acute epilepsy animal model constructed by the present application has stable effect and small individual difference; the multiple factors synergize with each other, and the constructed disease model is more accurate. The model exhibits a high success rate and stability in inducing classic symptoms of epilepsy (neuron damage, hippocampal sclerosis, glial cell proliferation, generalized tonic-clonic seizures, etc.), as well as anxiety, depression and cognitive impairment and other symptoms accompanying epilepsy.

[0018] 3. The present animal model of acute epilepsy, induced by a non-single factor, supports the multifactorial pathogenesis of acute epilepsy and better simulates the advantages of acute epilepsy in humans, providing an important theoretical basis for the development of new pharmaceutical agents for the effective treatment of acute epilepsy. It can not only be used to explore the scientific implications of multifactorial factors in acute epilepsy, but also provide an animal model that reflects the essence of the disease for the screening of new drugs.

[0019] 4. The present invention employs an induction method involving intravenous injection of 6-hydroxydopamine, intraperitoneal injection of IL-1β, and glycine. 6-hydroxydopamine is a neurotoxin. A certain dose of 6-hydroxydopamine can damage mice's neurons, leading to acute destruction of neurons in the limbic brain regions (amygdala, olfactory cortex, hippocampus, lateral septum, and thalamic nucleus) and degenerative changes in limbic structures. Intravenous injection of 0.5-1 mg / kg of 6-hydroxydopamine can significantly damage mice's neurons. The proinflammatory cytokine IL-1β is closely implicated in the development of epilepsy. Its expression is low in normal brain cells. IL-1β can affect the seizure threshold by altering neuronal excitability, thereby establishing an overexcited neuronal network and promoting epileptic seizures. Intraperitoneal injection of IL-1β at 6-8 μg / kg effectively induces epileptic seizures in mice. Simultaneously, intraperitoneal injection of glycine at 15-20 μg / kg one hour later synergizes with IL-1β, exacerbating its induction and leading to defects in axons, neurotransmitters, and dendrites in the mouse neuronal network. Intravenous injection of 6-hydroxydopamine, intraperitoneal injection of IL-1β, and glycine, all three agents synergize in the epileptogenic process, achieving a 1+1>2 effect from different perspectives. This tandem administration of these three agents significantly optimizes the induction of acute epilepsy in mice and facilitates the development of an acute epilepsy model in mice.

[0020] 5. Ultraviolet light stimulation of a certain wavelength can activate mouse neuronal cells, thereby achieving cell type and pathway specific activation, which is closely related to the onset of epilepsy. Ultrasonic treatment of a certain intensity can destroy neurons in the brain area of ​​mice and cause degenerative changes in some neuronal cells. In this application, 280-320nm ultraviolet light stimulation and 28-30kHz ultrasonic treatment are used, which are greatly beneficial to inducing the occurrence of acute epilepsy in mice. It not only consolidates the induction effect of the injected agent to a certain extent, but also further aggravates the pathological changes of neurons in the mouse brain.

[0021] 6. The present invention adopts the induction method of starvation treatment and acetic acid fumigation. In the late stage of modeling, mice are subjected to intermittent starvation treatment, and acetic acid fumigation is carried out at the same time as the starvation treatment, which can stimulate the mental state of mice, promote the inflammatory response of the mouse hippocampus tissue, and aggravate the pathological changes in the mouse brain. The starvation treatment and acetic acid fumigation in the last half month of modeling not only consolidate the induction effect of the early drug injection, ultraviolet light stimulation and ultrasonic treatment, but also increase the sensitivity of the mouse brain and aggravate the pathological reaction of the mouse brain to a certain extent. It plays a finishing touch role in this study and ensures a stable acute epilepsy animal model.

[0022] This study can provide a good theoretical support and model reference for in-depth analysis of the brain immune mechanism after acute epilepsy in humans and for the evaluation of new treatment methods. The research team has repeatedly verified the model many times, and the results are reliable. They have also used this model to evaluate the efficacy of a variety of drugs, verifying the application value of the model. This animal model exhibits the typical characteristics of acute epilepsy: neuronal damage, hippocampal sclerosis, glial cell proliferation, generalized tonic-clonic seizures, etc. This model can be used for basic research in the field of acute epilepsy and lay the foundation for experimental animals to explore the pathogenic mechanism of acute epilepsy. This study can provide a reliable animal model for the evaluation of the efficacy of acute epilepsy drugs, which has the advantages of low cost, stable model, simple operation, non-invasiveness, high success rate, and low animal mortality. DETAILED DESCRIPTION

[0023] A method for constructing an acute epilepsy model in mice, comprising the following steps:

[0024] (1) Animal selection: Select clean-grade adult male C57BL / 6 mice, weighing 18g-22g, aged 8 to 10 weeks, and housed in a cage with 12 hours of light and 12 hours of darkness, with free access to water and food. The housing temperature is 22℃ to 26℃.

[0025] (2) Drug injection: The model was established after the experimental mice were adaptively raised for two weeks; 6-hydroxydopamine 0.5-1 mg / kg was injected intravenously on the 1st, 5th and 15th day, and IL-1β 6-8 μg / kg and glycine 15-20 μg / kg were injected intraperitoneally on the 3rd, 8th and 20th day, respectively. IL-1β was injected first in each intraperitoneal injection, and glycine was injected 1 hour later.

[0026] (3) Ultraviolet light stimulation: An ultraviolet lamp with a wavelength of 280 to 320 nm was set in the mouse cage. The ultraviolet lamp was turned on for 10 minutes every morning during the modeling period.

[0027] (4), ultrasonic treatment: ultrasonic generator is arranged in the mouse cage, the ultrasonic generator generates ultrasonic wave with power of 1000W and frequency of 28-30 kHz, and the ultrasonic generator is started for 30 minutes in the afternoon every day.

[0028] (5), starvation treatment and acetic acid fumigation: after two weeks of modeling, the experimental mice are starved from the 15th day, and no food and water are provided to the mice, the starvation treatment is performed once every other day, and lasts for half a month, i.e. the 15th, 17th, 19th, 21st, 23rd, 25th, 27th and 29th days are starved, and the 16th, 18th, 20th, 22nd, 24th, 26th and 28th days are normally fed. The starvation treatment is performed at the same time as the acetic acid fumigation (i.e. the 15th, 17th, 19th, 21st, 23rd, 25th, 27th and 29th days are acetic acid fumigated), the acetic acid fumigation is that white vinegar and water are poured into a steamer in a ratio of 1:1, and the fumigation is performed twice a day, and each time for 10 minutes. After 29 days of modeling, the mouse acute epilepsy model is obtained.

[0029] After 29 days of modeling, the model is evaluated by observing the behavior of the mice, detecting the cognition by the Morris water maze experiment, observing the pathology, recording the electroencephalogram, detecting the inflammation level by the ELISA method, observing the neuron apoptosis by the TUNEL staining, and detecting the expression of P2X7 and NF-κB proteins in the hippocampal tissue by the Western blotting method (the blank control group is injected with normal saline and normally fed), and the results are as follows:

[0030] 1. Behavior observation:

[0031] The seizures are determined according to the Racine classification standard: 0, no convulsion; I, ear and facial convulsion; II, myoclonus without upright position; III, myoclonus with upright position; IV, general rigidity; and V, rigidity and myoclonus with loss of body position control. The mice with III or above seizures for 1 hour and in good condition after the seizures are removed are the successful mice of the status epilepticus model.

[0032] None of the mice in the blank control group had seizures. All the mice in the model group reached level I or above, including 4 mice at level I (4 / 60), 5 mice at level II (5 / 60), 6 mice at level III (6 / 60), 16 mice at level IV (16 / 60), and 29 mice at level V (29 / 60). Almost all the mice in the model group initially exhibited half-extended forelimbs, curled hind limbs, a prone body, wet-dog shakes, or immobility. Gradually, rhythmic facial muscle twitching, rhythmic nodding, unilateral or bilateral forelimb twitching, and rapid repeated head-throwing twitching appeared, and gradually intensified and spread to the forelimbs and hind limbs. Seizures, arching of the back, rigid tail, sudden jumping, and screaming occurred, followed by falling, gradually reduced convulsions, muscle relaxation, pale tail, dark red limbs, retracted scrotum, inability to crawl, and frequent urinary incontinence.

[0033] 2. Detection of cognitive function of mice by Morris water maze experiment

[0034] The positioning navigation experiment was performed as follows: the mice were placed in water, and the escape latency was the time for the mice to swim to the platform. Mice that did not reach the platform within 120 s should be guided to climb onto the platform. Training was performed for 6 days, and the escape latency on the 7th day was recorded. In the spatial exploration experiment, the platform was removed on the 8th day, and the mice were placed in the water again. The number of times the mice reached the platform was recorded.

[0035] The escape latency of the blank control group and the model group was (11.88±2.05) and (48.65±4.53), respectively. The number of times the platform was crossed was (6.85±0.70) and (3.11±0.28), respectively. Compared with the blank control group, the model group had a prolonged escape latency and a reduced number of times the platform was crossed.

[0036] 3. Pathological observation

[0037] Randomly selected mice were executed by cervical dislocation, and the brain was removed on an ice table and placed in paraformaldehyde for fixation. After craniotomy and brain removal, fixation was performed, followed by gradual dehydration, transparency, wax immersion, and paraffin embedding. After sectioning, hematoxylin-eosin staining was performed.

[0038] Hematoxylin-eosin staining showed that the neurons in the hippocampus of the blank control group were arranged tightly and regularly. In the model group, the hippocampal neurons were arranged irregularly, the intercellular space was enlarged, and swollen, degenerated, necrotic, and disintegrated cell bodies were observed. The volume was small, the cytoplasm was condensed and deeply stained, the nucleus was pyknosis, the nucleolus was unclear, the nuclei of dead cells were lysed, the cytoplasm was absent, the neurons in the CA1 region and the portal region were almost completely absent, the regular band-like arrangement was lost, a large number of grid cells and new capillaries appeared, and glial cell proliferation was significant.

[0039] 4. Electroencephalogram recording

[0040] The mouse limbs were fixed on the wood board with fine hemp rope, and the head was fixed with fine hemp rope. The needle electrode was inserted into the subcutaneous tissue of the forehead and both temples, and the ground wire was placed on the tip of the nose. Spike (spike) wave, spike (spike) slow wave and burst high amplitude rhythmic activity were used as epileptiform discharge.

[0041] The EEG of the blank control group was mainly 5-12 Hz activity, with amplitude of 20-50 μV, and no epileptiform discharge. The EEG of the mice with grade I seizure also had no obvious epileptiform discharge. The EEG of the mice with grade II and above seizures showed burst high amplitude rhythmic spike wave or spike slow wave, and the mice with status epilepticus showed persistent rhythmic spike wave, spike slow wave or high amplitude slow wave.

[0042] 5. Detecting the level of inflammation by ELISA method

[0043] IL-6, TNF-α, IL-1β, SOD and MDA levels were detected by ELISA method. The mouse brain tissue was placed in a homogenate tube, and the tissue was broken by a tissue homogenizer. The sample coating solution was extracted, and the remaining steps were strictly followed according to the instruction manual.

[0044] Compared with the blank control group, the IL-6, TNF-α, IL-1β and MDA levels in the model group were significantly increased, and the SOD level was significantly decreased.

[0045] 6. Observation of neuronal apoptosis by TUNEL staining

[0046] The paraffin sections were taken, washed and mounted. The remaining steps were performed according to the TUNEL kit. The hippocampal neuronal TUNEL positive cells were observed under a light microscope. The apoptosis of neurons was observed under a 200x microscope, and the apoptosis index was calculated as follows: black apoptotic cell number / cell total number x 100%.

[0047] The apoptosis indexes of the blank control group and the model group were (4.05±1.10)% and (43.12±3.58)%, respectively. Compared with the normal group, the apoptosis index of the model group was significantly increased.

[0048] 7. Detection of P2X7 and NF-κB protein expression in mouse hippocampal tissue by Western blotting (WB) method

[0049] The total protein of mouse hippocampal tissue was extracted for gel electrophoresis separation. After transfer, blocking, incubation of primary and secondary antibodies, β-actin was used as an internal reference, and QWin-image analysis software was used to analyze the P2X7 and NF-κB protein expression in hippocampal tissue.

[0050] The relative expression amount of P2X7 protein in hippocampus tissue of the blank control group and the model group was 0.18±0.02 and 1.35±0.28 respectively, and the relative expression amount of NF-κB protein was 0.36±0.04 and 1.24±0.15 respectively. The expression amount of P2X7 and NF-κB in hippocampus tissue of the model group was higher than that of the control group.

[0051] After repeated experiments, the experimental groups all showed the same results. The onset form and electroencephalogram activity of the mouse model constructed in the present study are consistent with those of human beings, the spiking discharge originates from one side of hippocampus, then rapidly spreads in the limbic system, and can spread to the cortex of the whole brain, causing corresponding seizures, and the form of abnormal electrical activity is also consistent with that of human epilepsy. Therefore, the mice in the experimental groups have typical symptoms of acute epilepsy, which meets the reliability and effectiveness of the judgment of the animal model of acute epilepsy, i.e. the cause of the disease, the symptom manifestation, and the pathophysiology, and the mouse model of acute epilepsy can be successfully obtained according to the construction method of the present application.

Claims

1. A method for constructing a mouse model of acute epilepsy, characterized by, Comprise the following steps: (1) animal selection: select clean level adult male C57BL / 6 mice, body weight 18g-22g, 8 weeks old-10 weeks old, feeding in 12 hours light, 12 hours darkness, free access to water and food mouse cage, the rearing environment temperature is 22℃-26℃; (2) injection of medicaments: after two weeks of adaptive feeding of experimental mice, modeling begins;Mice are intravenously injected with 6-hydroxydopamine 0.5-1mg / kg on the 1st, 5th, 15th day, and IL-1β 6-8μg / kg and glycine 15-20μg / kg are injected intraperitoneally on the 3rd, 8th, 20th day, IL-1β is injected first, and glycine is injected 1 hour later each time; (3) ultraviolet light stimulation: ultraviolet lamps are set up in the mouse cage, the ultraviolet lamps produce wavelengths of 280-320nm, and the ultraviolet lamps are turned on for 10 minutes every morning during modeling; (4) ultrasonic treatment: ultrasonic generators are set up in the mouse cage, the ultrasonic generators produce ultrasonic waves with a power of 1000W and a frequency of 28-30kHz, and the ultrasonic generators are turned on for 30 minutes every afternoon; (5) starvation treatment and acetic acid fumigation: after two weeks of modeling, the experimental mice are starved from the 15th day, no food and water are provided to the mice, starvation treatment is performed once every other day, and lasts for half a month, i.e. on the 15th, 17th, 19th, 21st, 23rd, 25th, 27th, 29th day, starvation treatment is performed, and on the 16th, 18th, 20th, 22nd, 24th, 26th, 28th day, normal feeding is performed;Starvation treatment is performed at the same time as acetic acid fumigation, the acetic acid fumigation is to pour white vinegar and water into a steamer in a ratio of 1:1, and fumigate in the morning and evening, each time for 10 minutes;After 29 days of modeling, the mouse acute epilepsy model is obtained.

2. The method of claim 1, wherein the method is characterized by, After 29 days of modeling, the model is evaluated by observing the behavior of the mice, detecting cognition by Morris water maze experiment, observing pathology, recording electroencephalogram, detecting inflammation level by ELISA method, observing neuron apoptosis by TUNEL staining, and detecting hippocampal tissue cell P2X7, NF-κB protein expression by Western blotting.