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The replication of animal models of neurological diseases is to use artificial methods to make animals under the action of certain pathogenic factors (physical, chemical, biological), causing a certain degree of damage to the animal's nervous tissue, organs or whole body, and causing some similar symptoms to human nervous system. Changes in the function, metabolism, morphological structure of diseases or various diseases can be used to study the occurrence and development of human diseases, and provide a theoretical basis for studying the prevention and treatment of human nervous system diseases.
Brain Case has built a variety of neurological disease models, such as Parkinson's (PD) model, Alzheimer's disease (AD) model, depression (Depression) model, epilepsy (Epilepsy) model, etc. Used for drug efficacy evaluation research on common neurological diseases.
Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease, with a huge number of patients. Data show that there are more than 2.7 million Parkinson's disease patients in my country, and more than 100,000 new patients are diagnosed every year. The prevalence rate for people over 65 years old is 1% to 2%, and the prevalence rate for people over 85 years old is even as high as 4%. As the elderly make up a larger share of the world's population, the incidence of the disease is expected to double over the next 20 years.
Parkinson's disease is characterized by resting tremor, bradykinesia, rigidity, and other symptoms that reduce quality of life, ultimately leading to severe disability due to the inability to control motor functions. It is characterized by early degeneration and death of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and widespread intracellular α-synuclein (α-Syn) aggregation.
Figure 1: Illustration of several areas of the brain adversely affected in Parkinson’s disease (PD)
Alzheimer's disease (AD) is a neurodegenerative disease that mostly affects the elderly. It was first discovered and named by German doctor Alois ALZHEIMER in 1907. According to statistics, there are approximately >50 million AD patients worldwide, which is expected to increase to ≥152 million by the middle of the 21st century, with total global medical expenses reaching US$818 billion, placing a heavy burden on the medical system and social economy.
AD is a very complex neurodegenerative disease. The pathological mechanism has not been clear yet, and there are several mainstream hypotheses. The cholinergic hypothesis believes that the degeneration of cholinergic neurons in the basal layer of the brain and the loss of cholinergic neurotransmission function in the cerebral cortex lead to the decline of cognitive function in AD patients. Currently, three cholinesterase inhibitors approved by the US FDA (Donepezil, galantamine, rivastigmine) used to treat AD are based on this hypothesis. The amyloid cascade hypothesis suggests that the onset of AD is due to the abnormal production and aggregation of Aβ amyloid in the brain, forming insoluble oligomers with neurotoxic effects. Another hypothesis is that the onset of AD is due to the dysfunction of phosphorylated tau protein (p-tau) in the cerebral subcortical and medial temporal limbic areas. The aggregation of Aβ protein (β-amyloid, Aβ) accelerates p-tau. Widespread protein-related neurodegeneration.
Depression, characterized by persistent mental depression and mood disorders, is one of the most common and prominent mental disorders in the world. Globally, the number of years lost todisability (YLD) due to disability caused by depression is as high as 76.4 million, accounting for 10.3% of all disease burden YLD, ranking first among disease burden factors. About 350 million people around the world suffer from depression, and the incidence rate in China is about 3.02%. Researchers believe that due to the influence of diagnosis methods, the depression situation among Chinese people is far underestimated. Its typical symptoms mainly include depression, slow thinking, loss of interest, eating and sleeping disorders, cognitive function impairment, and various other physical symptoms.
Over the years, in order to accurately simulate the occurrence and symptoms of depression, researchers have conducted in-depth research on animal models of depression in aspects such as environmental stress, social stress, neurobiochemistry, and genetic modification. The entry point of each model is different, and each has its own scope of application and limitations. The modeling methods of depression can be divided into four major categories, namely stress modeling, surgical modeling, and drug-induced modeling. Modeling and genetic modeling.
Epilepsy is one of the common diseases of the nervous system. Patients often present with sudden and brief abnormalities in movement, feeling, consciousness or mental state. Repeated disease attacks seriously affect the patient's life and psychology, and even damage cognitive function. Data show that the quality of life of patients with epilepsy is significantly lower than that of the normal population, and lower than that of patients with other chronic diseases, such as hypertension, diabetes, etc. According to epidemiological surveys, the annual prevalence rate of the general population is 5‰~7‰, and the prevalence rate of active epilepsy (attacks within 5 years) is 4.6‰. Currently, there are more than 9 million epilepsy patients in my country, of which 5 million~ There are 6 million patients with active epilepsy, and the number of new cases each year is 650,000 to 700,000. Its pathogenesis is very complex and has not been fully elucidated so far. Research in recent years has shown that epilepsy is closely related to ion channels, neurotransmitters, glial cells, contact transmission and gap junctions.
| Model | Modeling method | animal |
| Parkinson's model | Peripheral or intracerebral injection of MPTP | big/mouse |
| Injection of 6-OHDA into the striatal-nigral system | rat | |
| Expression of α-Synuclein by rAAV9X virus injection into the substantia nigra of the midbrain | rat | |
| Alzheimer's disease model | Brain positioning surgery for bilateral fornix-fimbria hippocampal incision | rat |
| Surgical method: insert 7mm sterile electrodes from the dura mater and stimulate with 1mA direct current (also called bilateral electrolysis of the basal ganglia model) |
rat | |
| Brain-localized injection of ibotenic acid/immunotoxin | rat | |
| intraperitoneal injection of scopolamine | rat | |
| Injection of Aβ solution into the hippocampus area of the brain | rat | |
| Stereotactic injection of okadaic acid into the brain | rat | |
| Transgenic animals (PS-1, PS-2 and apoE4, etc.) | big/mouse | |
| Brain-localized injection of immunotoxin to remove basal forebrain cholinergic cells | rat | |
| Epilepsy model | Injection of kainic acid (also known as kainic acid, KA) epilepsy model (systemic administration and brain administration) |
big/mouse |
| Injection of lithium chloride-pilocarpine (Lithium-Pilocarpine model) | big/mouse | |
| Brain-localized injection of kainate into amygdala ignition model | big/mouse | |
| Subcutaneous injection of pentylenetetrazole (pentylenetetrazole acute epilepsy model) | big/mouse | |
| depression model | forced swim test | big/mouse |
| tail suspension test | mouse | |
| DL-5-hydroxytryptophan (5-HTP) induction | mouse | |
| reserpine induction | mouse | |
| Increased toxicity of yohimbine | mouse | |
| High dose apomorphine antagonism | mouse | |
| Chronic moderate intensity stimulation model (electric foot shock, swimming in ice water, heat stress, tail clamping, water and food deprivation, day and night reversal) |
big/mouse | |
| New environment feeding inhibition experiment | big/mouse |
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