Abstract:Objective To establish models of an alcoholic fatty liver induced by a alcohol liquid diet and alcohol combined with a high fat diet in C57BL/6J mice in a short time and assess a more efficient model of an alcoholic fatty liver in mice by biochemical and histopathological method. Methods Twenty?four healthy male C57BL/6J mice acclimated for 2 weeks were randomly divided into four groups (n=6): maintenance diet group, liquid diet control group, alcohol liquid feed group and high fat diet group. Daily feed consumption and body weight were recorded. On day 16, the animals were sacrificed and serum transaminase activity, serum lipids, and blood glucose were measured. Paraffin?embedded sections and frozen sections of the liver were prepared and stained with HE and oil red O, respectively. Results Compared with the other three groups, the body weight of mice in alcohol liquid feed group showed a significant downward trend and the growth rate was negative. The caloric intake of high fat diet group was significantly lower than that of the other three groups. The liver weight and liver weight index of the liquid diet control group, alcohol liquid diet group and high fat diet group were significantly lower than those of the maintenance diet group. The biochemical Results showed that the levels of ALT, AST and TC in the alcohol liquid diet group were significantly higher than those in the maintenance diet group, and the blood glucose level was higher than that in the maintenance diet group. ALT, AST, TC and blood glucose in the alcohol liquid diet group were also higher than those in the liquid diet control group. Serum TC in the high fat diet group was significantly higher than that in the maintenance diet group, and AST and blood glucose were higher than those in the maintenance diet group. The blood glucose of high fat diet group was significantly higher than that of liquid diet control group. Pathological staining results showed that there was a large amount of lipid deposition in the liver of mice in the alcohol liquid diet group, followed by the high fat diet group. Conclusions The short?term Gao?Binge model and alcohol plus high fat diet model can successfully induce the corresponding biochemical and pathological characteristics of AFL in C57BL/6J mice, and the corresponding pathological indexes of Gao?Binge model group are more significant than the latter, which is suitable for the establishment of acute AFL model.

Abstract:Objective To investigate the role of the PINK1/ Parkin mitochondrial autophagy pathway in myocardial injury of chronic kidney disease, and the mechanism of Shenshuai recipe in the treatment of 5/6 nephrectomy CKD myocardial injury in rats. Methods Overall, 48 nephrectomized rats were randomly divided into six groups: sham then sacrificed. Heart tissue was collected, stained with HE, and observed under a light microscope. Autophagosomes and autophagic lysosomes were observed by transmission electron microscopy. PINK1, Parkin, P62, and LC3B mRNA levels were measured by RT?PCR. PINK1, Parkin, P62, and LC3B protein levels in nephrectomized rats were measured by Western Blot. Results Compared with the sham?operated group, CK?MB and hs?cTnI were significantly increased in the model group (P<0.01). Compared with the model group, benazepril group, low, medium, and high dose Shenshuai recipe groups were significantly decreased (P< 0.05). Compared with the sham operated group, myocardial tissue in the model group after nephrectomy was obviously disordered and displayed interstitial hyperplasia, vascular wall thickening, and glassy changes. There were no obvious abnormalities in Benazepril and low, medium, and high dose Shenshuai Recipe groups. Compared with the model group, the numbers of autophagosomes and autophagic lysosomes were increased significantly in low, middle, and high dose Shenshuai recipe groups(P< 0.01). Compared with the sham operated group, PINK1, Parkin, P62, and LC3B mRNA levels were significantly decreased in the model group(P< 0.05). Compared with the model group, PINK1, Parkin, P62, and LC3B mRNA levels were significantly increased in benazepril and high, medium, and low dose Shenshuai recipe groups(P< 0.05). Compared with the sham operated group, PINK1, Parkin, P62, and LC3B protein levels were significantly decreased in the model group (P< 0.01). Compared with the model group, PINK1, Parkin, P62, and LC3B protein levels were significantly increased in Benazepril and low?, medium?, and high?dose Shenshuai recipe groups (P< 0.01). Conclusions The PINK1/ Parkin mitochondrial autophagy pathway in myocardial cells of rats with myocardial injury caused by 5/6 nephrectomy was inhibited. Shenshuai recipe enhanced mitochondrial autophagy by activating the PINK1/ Parkin mitochondrial autophagy pathway, and played a protective role in myocardial cells. Among the groups, the highest dose of Shenshuai recipe had the most significant effects on mitochondrial autophagy intensity.

Abstract:Objective To establish a humanized mouse model of depression by fecal bacteria transplantation and evaluate the model. Methods The feces of depressed and healthy people in the climacteric period were transplanted into simulated sterile mice. Sixty C57BL/6 mice were divided into blank group, depressed fecal bacteria transplantation (FMT?P) and healthy fecal bacteria transplantation (FMT?H)a groups. The blank group (20 mice) was only fed an ordinary diet. The FMT?P group (20 mice) was pretreated with an antibiotic cocktail, and then the model was established by fecal bacteria transplantation in the depressed population. The FMT?H group (20 mice) was administered the antibiotic cocktail, and then the model was established by fecal bacteria transplantation in the healthy population. Each group was continuously fed for 28 days. The general conditions and behavioral tests of mice were observed by tail suspension and new environment feeding tests, the serum levels dopamine (DA), norepinephrine (NE), 5?hydroxytryptamine (5?HT), and γ?aminobutyric acid (GABA) were determined by ELISA, and colon histopathology was observed by HE staining. Results Compared with the blank control group, the body mass of the FMT?P group was increased slowly, the time of depression was significantly prolonged, the feeding time was significantly decreased, and there were depression symptoms such as decreased activity, disheveled and yellow hair, shedding fur easy to fall off, and mental fatigue. The serum levels of GABA, 5?HT, and DA in FMT?P group the group were significantly lower than those in the blank control group. Microscopically, colonic tissue was disordered, glands enlarged glands were increased, and local inflammatory cells had infiltrated. Conclusions The combination of antibiotic cocktail therapy and fecal bacteria transplantation establishes a humanized mouse model of depression.

Abstract:Objective Current research and treatments for the pathogenesis of chronic heart failure (CHF) are limited. In order to better study its pathogenesis, this paper optimized the preparation method of isoproterenol (ISO)?induced chronic heart failure rat model. Methods SD male rats were divided into 4 groups, and rats in model A were injected with ISO 5 mg/ (kg·d) continuously for 10 days; rats in model B were injected with ISO 2.5 mg/ (kg·d) on the first 3 days and 5 mg/ (kg·d) on the last 9 days; rats in model C were given 15 mg/ kg of pentobarbital sodium on day 1 and ISO 1?? 25 mg/ kg on day 2 and 3, and 2.5 mg/ (kg·d) on day 2 and 3, and 5 mg/ (kg·d) on the last 9 days, with 30 min interval between 2 injections per day from day 2. The control group was given equal amounts of saline. The successful establishment of the model was verified by echocardiography, pathology testing and fluorescence quantitative PCR. Results Mortality rates were 80%, 60%, and 40% in model groups A, B, and C, respectively. Compared with the control group, the left ventricular short axis shortening and ejection fraction were significantly lower in model group C (P<0.001). Rats in group C had disturbed myocardial cell arrangement, significantly increased collagen type Ⅰ and Ⅲ expression (P< 0.05), and significantly upregulated expression levels of fibrosis indexes COL1A1, COL3A1, FN1 and ACTA2 mRNA (P< 0.05), while the levels of serum N?terminal pro?B type natriuretic peptide (NT?pro BNP) and triglycerides were significantly increased (P< 0.05). Conclusions Injecting anesthetics to keep the rats in a semi?conscious state, increasing the daily injection dose and decreasing the single injection dose in a gradient can reduce the mortality rate, which can provide a new idea and a new approach for establishing a CHF rat model.

Abstract:Objective To explore a modeling method of the combination of disease and syndrome of knee osteoarthritis KOA based on the pathogenesis theory of “Deficiency, Stasis and Toxicity” in (KOA). Methods Overall, 24 New Zealand white rabbits were randomly divided into a SHAM group (n= 8), MODEL group (n= 8), and TCM + MODEL group (n= 8). The SHAM group was fed normally. The MODEL group was established by plaster fixation. In the TCM + MODEL group, we hydrocortisone gavage and TCM etiological factors (wind, cold, and wet) were combined based on plaster fixation. After 6 weeks of modeling, each group was comprehensively evaluated, including the TCM syndrome and sign score, knee imaging, articular surface gross observation, Saffron O?solid green staining, blood and articular fluid IL?6 and TNF?α levels, hemorheology, and serum CORT, T, SOD, and MDA levels. Results The TCM symptom and sign score, imaging score, gross observation score, Mankin score, levels of IL?6 and TNF?α in joint fluid, hemorheology indexes (PV and RCAI), and serum MDA in the TCM + MODEL group were significantly higher than those in SHAM and MODEL groups (P< 0.05). Compared with the MODEL group, serum CORT, T, and SOD were significantly decreased in the TCM + MODEL group (P< 0.05), while serum IL?6 and TNF?α were not significantly different (P> 0.05). Conclusions By plaster fixation combined with the model of kidney deficiency syndrome gavage with hydrocortisone and etiological treatment with traditional Chinese medicine, including wind, cold, and wet, we reproduced the combination of disease and syndrome model of KOA with the characteristics of “Deficiency, Stasis and Toxicity”, which provides an experimental basis for further research on syndrome differentiation and treatment of KOA by traditional Chinese medicine.

Abstract:Objective To establish an animal model of myocardial fibrosis induced by iron overload. Methods Eighteen Bama minipigs were randomly divided into an experimental group (n= 15) or control group (n=3). An iron dextran solution was intramuscularly injected every seven days. The first dose was 400 mg/ kg, and the other doses were 200 mg/ kg. The control group was injected with the same volume of normal saline. One to two Bama minipigs were randomly euthanized 6 days after injection of iron. Cardiac tissue sections were used for myocardial collagen volume fraction (CVF), semiquantitative myocardial iron, cardiac iron concentration (CIC) measurements. Results With the increase in the number of injections, CIC in the experimental group showed an upward trend, and the proportions of myocardial iron, and CVF (r= 0.957, r= 0.971, r= 0.957, P< 0.001). CIC was highly correlated to CVF (r=0.924, P< 0.001), and myocardial iron was highly correlated to CIC and CVF (r= 0.973, P< 0.001; r= 0.944, P< 0.001). Conclusions A miniature pig model of myocardial fibrosis was established by intramuscular injection of 400 mg/ kg iron dextran as the first dose and 200 mg/ kg iron dextran as the other doses. More iron particles deposited in the myocardium led to more severe myocardial fibrosis.

Abstract:Objective To compare the pathological characteristics and transcriptome differences among three rat models of myocardial hypertrophy (CH) induced by transverse aortic constriction (TAC), isoproterenol (ISO), and spontaneous hypertension (SHR). Methods Male SD and SHR rats (control group: WKY) were used to establish three models. For the TAC experiment, SD rats were divided into a sham group (n= 5) and TAC group (n= 14). Rats in the TAC group underwent TAC surgery and the sham group underwent a sham operation. Each group of rats were fed for 5 weeks after the operation. For the ISO experiment, SD rats were randomly divided into a control group (C) (n= 5) and ISO group (n= 11). Rats in the ISO group received multiple subcutaneous injections of 5 mg/ (kg·d) ISO on the back of the neck, whereas the control group was injected with the same dose of saline twice daily for 10 days. For the spontaneous hypertension?mediated CH experiment, SHR rats were considered as the model group (n= 5) and WKY rats as the control group (n= 5). All rats were normally fed to 16 weeks of age. Echocardiography was performed and plasma ANP levels were measured to determine whether the CH rat model was established successfully. Then, survival rates, blood pressure, hemodynamics, and the cardiac mass index were calculated. Heart tissues were stained with HE, Masson, and wheat germ agglutinin (WGA). Transcriptome sequencing was performed in myocardial tissue to screen differentially expressed genes and analyze their pathways. The sequencing result were verified by quantitative real?time PCR ( qRT?PCR). Results Plasma ANP in each model group was significantly higher than that in the control group (P< 0.05). IVSd, IVSs, LVPWd, and LVPWs in TAC and ISO model rats and LVSd in SHR rats were significantly increased (P< 0.05), while LVIDd and LVIDs were significantly decreased (P< 0.05) compared with those in the control group. The survival rates of model rats in each group were 100% for SHR, 81.82% for ISO, and 35.71% for TAC. Compared with control groups, the blood pressure of model rats in TAC and ISO groups was significantly decreased (P< 0.05), whereas that of the SHR group was significantly increased (P< 0.01). HW/ BW and LVW/ BW ratios in each model group were increased significantly (P< 0.05). Hemodynamics showed that HR, LVESP, LVEDP, and dP/ dtmax were significantly decreased in model rats of TAC and ISO groups (P< 0.01), whereas all indexes in SHR rats were significantly increased (P<0.01). The myocardial tissue of TAC and SHR model rats showed a heterogeneous network of reactive interstitial fibrosis, whereas ISO rat myocardial tissues had a large area of repaired interstitial fibrosis. The cross?sectional area of the myocardium in TAC and ISO groups was increased significantly (P< 0.05), but there was no significant difference in SHR rat. In total, 175, 568, and 279 differentially expressed genes were identified by transcriptome sequencing in TAC, ISO, and SHR models, respectively. Autophagosome, cancer?related signaling pathway, and PI3K/ AKT pathway were co?enriched in the three model groups, while drug response, relaxin signaling, and JAK/ STAT signaling pathways were only enriched in TAC, ISO, and SHR model groups. qRT?PCR result were consistent with the transcriptome sequencing data. Conclusions CH was successfully established in TAC? and ISO?treated rats and spontaneously hypertensive rats. The survival rate, blood pressure, hemodynamics, degree of myocardial hypertrophy, histopathological characteristics, and gene expression profiles in CH model rats were influenced by various induced factors.

Abstract:Objective To compare three kinds of yang?deficiency STC rat models by a combination of disease and syndrome evaluation to provide an ideal experimental animal model for TCM prevention and treatment of this disease. Methods Sixty?four SD rats were divided into blank and model groups. The rats were treated with loperamide hydrochloride combined with 0℃ ice water by gavage (M?1 group), loperamide hydrochloride combined with dahuang decoction (M?2 group), and white vinegar and 0℃ ice water by gavage alternately + loperamide hydrochloride by gavage (M?3 group) (16 rats in each group) to establish the three yang?deficiency slow transit constipation rat models. The blank group (n= 16) was administered the same volume of distilled water by gavage. Model groups were established by the corresponding method. The general condition of rats was observed during modeling. Rectal temperature, food intake, voluntary activity, stool Bristol score, and water content were measured at fixed times every week. After establishing the model, the discharge time of the first black stool and the intestinal propulsion rate were measured. Rat colon pathological changes were observed by HE staining. Colon mucous changes were assessed by PAS staining. Colon 5?HT, VIP, and SP were analyzed by ELISA and IHC. Results Blank group rats before and after building without exception. After modeling, rats in each model group showed listlessness, lethargy, and crouching. Some rats died during modeling. Mortality was in the order of M?3 group > M?2 group > M?1 group. Compared with the blank group, the anal temperature, food intake, and voluntary activity of each model group showed a downward trend during modeling. The model groups were compared with the blank group as follows: M?1 group: building 3 weeks of food intake, autonomous activity was obviously decreased (P<0.01), building 4 weeks of rectal temperature and fecal water content were significantly decreased (P< 0.01), building 5 weeks of Bristol stool scale was significantly decreased (P< 0.01). M?2 Group: building 3 weeks of rectal temperature, food intake, and autonomous activity were significantly decreased (P< 0.01), building 6 weeks of the Bristol stool scale and fecal water content were significantly decreased (P< 0.01). M?3 Group: building 1 week of autonomous activity was decreased significantly (P< 0.01), building 2 weeks of food intake significantly decreased (P< 0.01), building 4 weeks of rectal temperature, Bristol stool scale, and fecal water content were significantly decreased (P< 0.01). HE staining showed no obvious pathological changes in the colon of rats in each group after modeling. PAS staining showed that the mucus layer thickness in the colon of rats in each model group was significantly reduced (M?3 < M?1 < M?2). Compared with the blank group, the first black stool excretion time in the model groups was increased, and the intestinal propulsion rate, and 5?HT and SP in the colon were significantly decreased (P< 0.01). VIP in the colon of M?1 group was significantly increased (P< 0.01). Conclusions The STC model of yang?deficiency can be established by the three modeling method. The rat model established by intragastric administration of loperamide hydrochloride combined with 0℃ ice water has the advantages of low mortality, good safety, stable yang?deficiency syndrome, obvious changes in stool characteristics, and significant pathological changes in intestinal motility. It is an ideal model to study the STC pathogenesis of yang?deficiency and the effect of traditional Chinese medicines.

Abstract:Objective To study the anti?tumor effects and mechanisms of celecoxib and pentoxifylline on Lewis lung carcinoma (LLC) in mice. Methods Mouse tumor models were established by subcutaneously injecting cultured LLC cells, which were divided into two groups. The control group was administered solvent, and the experimental group was administered celecoxib and pentoxifylline. The tumor size and volume were measured twice a week to observe the tumor inhibitory effect of celecoxib and pentoxifylline. Pathological changes were observed by immunohistochemistry, and the expression levels of COX?2, Bid and Caspase?9 proteins were measured by Western Blot. Results Celecoxib and pentoxifylline had an inhibitory effect on LLC in mice. The median survival of the experimental group was higher than that of the control group, which was related to inhibition of angiogenesis and induction of LLC cell apoptosis. Conclusions Combined celecoxib and pentoxifylline inhibited LLC growth in mice by suppressing angiogenesis and inducing tumor cell apoptosis.

Abstract:Objective To investigate the effect of combined sodium creatine phosphate and trimetazidine on echocardiography and cardiac serology in rats with alcoholic cardiomyopathy. Methods A rat model of alcoholic cardiomyopathy was established by chronic alcohol gavage. After successful modeling, rats were randomly divided into creatine phosphate (CPS), trimetazidine (TMZ), creatine phosphate + trimetazidine(CPS + TMZ) group, normal saline group (NS), and alcohol (AL) groups. The study was conducted for 8 weeks. Echocardiography was used to measure left ventricular end?diastolic diameter(LVEDd), ventricular septal end?diastolic thickness(IVSDd), left ventricular posterior wall end?diastolic thickness(LVPWDd), and left ventricular ejection fraction(EF). Serum creatine kinase CK?MB, high? sensitivity troponin I (Hs?TnI), lactate dehydrogenase (LDH), and amino?terminal brain natriuretic peptide (Nt?proBNP) were also measured. Results (1) Compared with AL and NS groups, LVEDd was decreased, EF was increased, and CK?MB, Hs?TnI, and LDH were decreased in CPS and TMZ groups. (2) Compared with CPS and TMZ groups, LVEDd was decreased, EF was increased, and CK?MB, Hs?TnI, LDH, and Nt?proBNP were decreased in the CPS + TMZ group. (3)There was no statistical difference in each index between CPS and TMZ groups. Conclusions Both creatine phosphate and trimetazidine have a therapeutic effect on alcoholic cardiomyopathy, and their combined effect is better than that of either alone.

Abstract:Objective To investigate the expression and significance of hypoxia?inducible factor?1α (HIF?1α), OPN, IL?1β, TNF?α, MMP?13, and NGF proteins in SD rats with knee osteoarthritis KOA induced by monosodium and model (KOA) groups. On day 0, the rats were anesthetized with sodium pentobarbital, and 50 μL of normal saline containing 2 mg of MIA was injected into the joint cavity of the KOA group through the infrapatellar ligament of the right knee. In the sham group, 50 μL sterile saline was injected into the knee joint cavity. SD rats were euthanized by overdosed anesthesia on days 0, 3, 7, 10, and 14 after measuring the diameter of the right knee joint and the weight?bearing capacity. Cartilage and synovial tissue were collected. Synovial tissues were primary cultured, and the purity and activity of fibroblast?like synoviocytes (FLSs) were assessed, and FLSs were treated with dexamethasone. Western Blot was used to detect HIF?1α, osteopontin (OPN), interleukin?1β (IL?1β), tumor necrosis factor?α (TNF?α), matrix metalloproteinase?13 (MMP?13), and nerve growth factor (NGF) proteins. Results Compared with the Sham group, HIF?1α, OPN, IL?1β, and TNF?α expression was increased at 3 days after injection of MIA into the knee cavity and showed an increasing trend. The transverse diameter of the knee cavity in the MIA group was significantly larger than that in the Sham group on days 7 and 14 after palpation. On day 3 after injection of MIA into the knee cavity of rats, the weight bearing capacity of the right hind limb continued to be < 26%, which was significantly lower compared with the Sham group. Primary FLSs were successfully isolated by 0.2% type Ⅰ collagenase digestion. After treatment of FLSs from KOA rats with dexamethasone, secretion of proinflammatory factors and expression of MMP?13 and NGF proteins were decreased significantly. Conclusions HIF?1α, OPN, IL?1β, TNF?α, MMP?13, and NGF play major roles in cartilage and synovial inflammation, cartilage degradation, matrix destruction, and joint pain. They are important targets for joint pain management, regulation of inflammatory responses, and inhibition of cartilage degradation and matrix destruction, and the development of novel OA analgesics.

Abstract:The comorbidity of drug abuse and human immunodeficiency virus (HIV) infection has attracted much attention. Drug abuse is a promoter of HIV transmission. It also aggravates the viral load in the central nervous system and accelerates the progression of HIV?associated neurocognitive disorders. This article focuses on the commonly used animal models related to HIV infection, such as non?human primates, rodents, and felines, analyzes their limitations and advantages, and summarizes the latest research progress of animal models related to HIV infection in drug abuse.

Abstract:Colorectal cancer has the second highest incidence in China. The pathogenesis of colorectal cancer is complex, and prevention and treatment require improvement. To reveal the tumorigenesis mechanism of colorectal cancer, a preclinical animal model should be established. Compared with carcinogenic induction and xenograft models, the genetically engineered animal model is a powerful experimental tool to simulate the genetic mutations of colorectal cancer patients. Since establishment of ApcMin/ + mice, the most representative spontaneous colorectal cancer model, researchers have been attempting to establish genetically engineered mouse models of colorectal cancer with high clinical similarity. In this review, we discuss the role of Apc gene mutations in tumorigenesis of colorectal cancer, and focus on the characteristics of mouse colorectal cancer models established by various combinations of genetic mutations in terms of pathological morphology, invasion, and metastasis. This will provide a reference for colorectal cancer research to select ideal experimental models.

Abstract:Mitochondria possess their own genome to maintain mitochondrial functions. Modification of mitochondrial DNA (mtDNA) provides important insights into gene functions, disease mechanisms, and therapeutics. However, the available tools for mtDNA editing are relatively limited because of the nature of the unique environment where mtDNA resides and the mechanism of DNA damage repair in mitochondria. With the rapid progress of nuclease and base?editing technologies in recent years, mitochondrially targeted nuclease tools and base editors have been developed, providing powerful tools for mtDNA editing. In this review, we summarize the recent progress of a series of tools developed for targeted editing of animal mtDNA and their applications in biomedicine, focusing on DdCBE (DddA?derived cytosine base editor), and provide a brief outlook on the existing problems and application prospects of mtDNA editing to provide a useful reference for the development of novel tools for mitochondrial genome editing and their wider applications in basic research, disease modeling, and clinical therapeutics.

Abstract:The golden hamster has been used as an animal model to study human diseases for more than 60 years, such as COVID?19 and metabolic diseases, and for safety evaluation of vaccines and therapeutic drugs. In accordance with the regulations of the WTO, golden hamsters used for vaccine production and verification must have a microbe control grade of specific pathogen free, but conventional animals are commonly used domestically. Therefore, it is imperative to improve the microbial grade of golden hamsters through sterile Cesarean section. In this review, we broadly discuss the applications of golden hamsters in the study of COVID?19 and metabolic diseases, and the research progress of sterile Cesarean section.

Abstract:Laboratory animals, as substitutes for suffering, have made important contributions to the development of medical life sciences for humans. Although various initiatives and regulations of the welfare and ethics of laboratory animals are continually being proposed and applied worldwide, because the demand and use of laboratory animals have been continuously increasing, the contradictions and controversy of laboratory animal welfare and ethics have become more prominent. Laboratory animal welfare ethics in our country were carried out relatively late. Therefore, the development of these ethics is necessary and urgent. At present, the laws and regulations of our country should be improved by referring to international standards and requirements, and combining them with our culture and current situation. Accelerating promotion of welfare ethics certification and evaluation starting from the laboratory animal industry, improving ethical review and evaluation, realizing the supervision of the whole process gradually, promoting the work responsibilities and status of veterinarians, and strengthening the education and awareness of practitioners will implement practical benefits for the welfare and rights of laboratory animals.

Abstract:Traumatic brain injury (TBI) is the destruction of normal brain functions and/ or pathological injury of brain tissue caused by external force. Because of the irreversible loss of functional neurons and nerve tissue damage, the central nervous system has difficulty repairing and regenerating after trauma, and the prognosis of TBI patients has serious sequelae. The existing TBI models cannot represent the characteristics of the human brain. Although many preclinical studies of TBI therapy have been successful, few have led to clinical translation. As a self?assembled 3D tissue with a collection of stem cells and organ?specific cell types, brain organoids simulate the structure and function of the natural brain to a certain extent. They effectively resolve the limitations of tissue acquisition in the human central nervous system and the mismatch of biological characteristics between humans and animals in TBI research. Therefore, in this review, we summarize the generation, characteristics, and application of brain organoids as TBI models and focus on the research progress of brain organoids simulated in vitro and chimeric animal models with TBI based on human pluripotent stem cells to provide new ideas for the application of brain organoids in the research and treatment of TBI injuries.