Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecul...Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.展开更多
Neurodegenerative diseases are increasing in prevalence due largely to aging populations worldwide and improved medical care for the elderly.Currently approved drugs can reduce some of the symptoms of neurodegenerativ...Neurodegenerative diseases are increasing in prevalence due largely to aging populations worldwide and improved medical care for the elderly.Currently approved drugs can reduce some of the symptoms of neurodegenerative diseases but cannot cure them.Inflammation is involved in the development and progression of neurodegenerative diseases,and oxidative stress is implicated in neurodegeneration associated with cognitive decline and age-related cognitive impairment.Polyphenols such as curcumin,quercetin,and resveratrol possess potent anti-inflammatory and antioxidant properties.Nanoformulations of curcumin and quercetin can optimize their pharmacological effects in the treatment of neurodegenerative diseases.Nanocarriers play a crucial role in delivering drugs across the blood-brain barrier,thereby lowering the risk of peripheral side effects.Various nanoforms have been developed to induce bioavailability and solubility of curcumin and quercetin,including nanoparticles and nanoemulsions.The studies reviewed included 17 using curcumin nanoformulations and seven with quercetin nanoformulations and were tested in widely used animal models of Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and multiple sclerosis.Many of the curcumin and quercetin nanoformulations brought about improvements in learning and memory in behavioral tests of Alzheimer’s disease models and were effective in reducing oxidative stress in the brain.Both nanocurcumin and nanoquercetin decreased the levels of inflammatory markers in the brain.Nanocurcumin formulations improved motor behavior,gait,and memory in Parkinson’s disease models and increased dopaminergic neurons in the striatum and substantia nigra.Furthermore,nanocurcumin improved locomotor activity,memory,and learning,and the number of dendrites of medium spiny neurons in Huntington’s disease models.Nanocurcumin formulations decreased oxidative stress and inflammation in a model of demyelination.Several important limitations were identified in the studies reviewed and these need to be considered in future studies.Also,clinical trials could be performed using the currently available nanoforms of curcumin and quercetin.展开更多
Background:This study aims to explore the establishment of an animal model of car-diac injury induced by trimethylamine-N-oxide(TMAO),a metabolite secreted by gut microorganisms,and to investigate its application in m...Background:This study aims to explore the establishment of an animal model of car-diac injury induced by trimethylamine-N-oxide(TMAO),a metabolite secreted by gut microorganisms,and to investigate its application in moderate-intensity continuous training(MICT)intervention.Methods:C57BL6/J mice were randomly divided into four groups:normal mice(Nor,n=15);mice administered TMAO(TMAO,n=15);mice undergoing(Nor+MICT,n=15);mice undergoing(MICT)and administered TMAO(TMAO+MICT,n=15).Mice in the TMAO and TMAO+MICT groups received daily gavage of high-dose TMAO for 8 weeks,whereas those in the Nor+MICT and TMAO+MICT groups underwent MICT for 8 weeks(60 min per session,5 days per week,at 50%maximal running capacity).Cardiac function was evaluated using ultrasound,myocardial histology was examined using hematoxylin and eosin(HE)staining,and nuclear magnetic resonance(NMR)-based metabolomics was employed for multivariate statistical and metabolic pathway analyses.Results:Relative to the Nor group,TMAO-treated mice exhibited significant weight loss,elevated heart rate,and reduced ejection fraction and left ventricular fractional shortening,indicating cardiac impairment.Importantly,the TMAO+MICT group dem-onstrated significant improvements in these parameters compared to the TMAO group,alongside distinct alterations in myocardial metabolic profiles.TMAO altered five metabolic pathways relative to controls,whereas MICT induced significant changes in three pathways in TMAO-treated mice.Conclusion:Eight weeks of high-dose TMAO administration induced significant cardiac dysfunction in mice,which was effectively mitigated by MICT intervention.Consequently,this animal model serves as a valuable tool for investigating the mecha-nisms underlying the impact of MICT on cardiovascular diseases.展开更多
Background:The traditional method of heterotopic abdominal heart transplantation(HTx)involves crossclamping the inferior vena cava,which inevitably leads to bilateral lower limb ischemia(LI).This study first aimed to ...Background:The traditional method of heterotopic abdominal heart transplantation(HTx)involves crossclamping the inferior vena cava,which inevitably leads to bilateral lower limb ischemia(LI).This study first aimed to investigate the impact of LI on renal function in rats subjected to unilateral nephrectomy(UNx).Second,a modified method utilizing renal vessel-assisted anastomosis in rats with left UNx was compared with the traditional method for abdominal HTx.Methods:Male Sprague-Dawley rats were utilized as subjects for both experimental phases.In experiment 1,the animals were divided into four groups:sham operation group;LI group-rats undergoing occlusion of the abdominal aorta and vena cava below the renal vessels;UNx group-rats with left UNx;and LI+UNx group.All operated animals were monitored for up to 7 days for biochemical markers,renal histopathology,and survival rates.In experiment 2,we introduced the renal vessel-assisted method as the experimental group and compared it against the traditional method as the control within rat heterotopic HTx models.We assessed operative characteristics,echocardiography results,histological findings,and graft survival.Results:First,LI resulted in acute kidney dysfunction characterized by a decrease in 7day survival rates and creatinine clearance rates in both the LI and LI+UNx groups compared to the sham operation and UNx groups.Particularly,histopathological damage in the kidney and liver did not exhibit significant effects during this period.Second,the implementation of the renal vessel-assisted method significantly reduced bleeding volume at suture sites and enhanced the 7day survival rate compared to the traditional method.Conclusion:Acute kidney injury was induced by LI postoperation in treated rats.The renal vessel-assisted method demonstrated its effectiveness as a superior alternative that mitigates complications associated with the traditional method.展开更多
Background:Healthy non-pharmacological lifestyle factors,such as regular physical exercise and dietary supplementation,have been shown to significantly improve cognitive outcomes over time compared to a more sedentary...Background:Healthy non-pharmacological lifestyle factors,such as regular physical exercise and dietary supplementation,have been shown to significantly improve cognitive outcomes over time compared to a more sedentary lifestyle and poor diet.Furthermore,exercise may serve as a potential protective factor in attenuating the effects associated with cognitive decline that are characteristic of neurodegenerative disorders,such as Alzheimer's disease(AD).Evidence indicates that certain dietary interventions can also attenuate the effects of neurodegeneration and positively impact longevity.Supplementation with polyphenols such as ellagic acid(EA),which is abundant in pomegranate juice,may help provide neuroprotective and longevity benefits.Methods:This study examined the potential protective potential of EA and exercise and provides insight into the combined use of a polyphenol-rich diet and exercise to enhance behavioral outcomes and lifespan in a transgenic Drosophila melanogaster(fruit fly)model of AD with the Aβ_(42) gene.Results:Fruit flies subjected to a 120-minute exercise regimen performed better on a climbing assay than flies that did not exercise.Conversely,flies that exercised for 30 min passed marginally more trials on a learning and memory assay using an aversive stimulus than flies that did not exercise,whereas both groups performed better than flies subjected to the more intense exercise condition.Conclusion:These results suggest a hormetic effect of exercise regarding memory performance.Finally,flies fed a low dose of dietary EA(0.24 mg/mL)lived significantly longer than flies fed the control diet or higher concentrations of EA,again suggesting a hormetic effect of EA on longevity.展开更多
BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models ...BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.展开更多
The incidence of benign airway stenosis(BAS)is on the rise,and current treatment options are associated with a significant risk of restenosis.Therefore,there is an urgent need to explore new and effective prevention a...The incidence of benign airway stenosis(BAS)is on the rise,and current treatment options are associated with a significant risk of restenosis.Therefore,there is an urgent need to explore new and effective prevention and treatment methods.Animal models serve as essential tools for investigating disease mechanisms and assessing novel therapeutic strategies,and the scientific rigor of their construction and validation significantly impacts the reliability of research findings.This paper systematically reviews the research progress and evaluation systems of BAS animal models over the past decade,aiming to provide a robust foundation for the optimized construction of BAS models,intervention studies,and clinical translation.This effort is intended to facilitate the innovation and advancement in BAS prevention and treatment strategies.展开更多
Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better appro...Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better approximate clinical reality,taking the case of doxorubicin treatment,we utilized an orthotopic transplant and resection(OtR)strategy to systematically assess the effects of neoadjuvant chemotherapy,adjuvant chem-otherapy,and their combination on tumor growth,recurrence,and malignant progression.Results:Surprisingly,none of the treatments improved mouse survival,with adjuvant therapy even shortening it.Although neoadjuvant chemotherapy delayed preopera-tive tumor growth,and all regimens reduced recurrence rates,none effectively pre-vented metastasis.Furthermore,all treatment groups exhibited weight loss,indicative of chemotherapy-induced cachexia.Conclusions:Collectively,these findings demonstrate that reduced tumor growth in preclinical mouse models does not necessarily translate into overall survival benefit.Our results emphasize the critical importance of prioritizing metastasis prevention over tumor growth inhibition as a key efficacy endpoint in antitumor drug evaluation.展开更多
This study summarizes the theoretical basis,modeling strategies,pathological mechanisms,and therapeutic advances related to high-altitude qi-deficiency and blood-stasis pattern.Traditional concepts such as“qi drives ...This study summarizes the theoretical basis,modeling strategies,pathological mechanisms,and therapeutic advances related to high-altitude qi-deficiency and blood-stasis pattern.Traditional concepts such as“qi drives blood”and“deficiency leads to stasis”closely align with modern evidence demonstrating that hypoxia disrupts energy metabolism,impairs microcirculation,and amplifies inflammation and oxidative stress.Current animal models commonly use hypobaric hypoxia combined with fatigue loading,dietary restriction,ice-water stimulation,or adrenaline injection to mimic the combined effects of qi deficiency,blood stasis,and hypoxic injury.These composite approaches reproduce systemic abnormalities,including reduced arterial oxygen partial pressure,increased blood viscosity,impaired cardiac and pulmonary function,microcirculatory obstruction,and mitochondrial dysfunction.Enhanced inflammatory signaling,oxidative stress,and disturbances in metabolic and epigenetic networks further characterize the pattern.The findings indicate that its pathogenesis arises from multi-system,multi-target interactions rather than a single pathway.Representative herbal formulas,such as Buyang Huanwu decoction,Xuefu Zhuyu decoction,and prescriptions rich in Astragalus membranaceus(Fisch.)Bunge(A.membranaceus,Huang qi)or Salvia miltiorrhiza Bunge(S.miltiorrhiza,Dan Shen)have demonstrated the ability to improve energy metabolism,attenuate endothelial injury,enhance microcirculation,and suppress inflammation through network-level regulation.Future research should focus on standardizing exposure parameters,developing quantitative syndrome evaluation systems,and integrating multi-omics,systems biology and artificial intelligence to improve model reproducibility and mechanistic precision.These efforts may help establish objective criteria for high-altitude qi-deficiency and blood-stasis pattern and support the development of targeted therapeutic strategies.展开更多
A lupuslike condition induced by intraperitoneal administration of pristane(2,6,10,14 tetramethylpentadecane)in mice is widely used as a model of systemic lupus erythematosus(SLE).Due to their phylogenetic distance fr...A lupuslike condition induced by intraperitoneal administration of pristane(2,6,10,14 tetramethylpentadecane)in mice is widely used as a model of systemic lupus erythematosus(SLE).Due to their phylogenetic distance from humans,murine models are not always suitable tool for studying the specific activity of therapeutic agents and the pathogenesis of SLE.In order to overcome speciesspecific limitations of murine models,this approach was tested in nonhuman primates-cynomolgus monkeys(Macaca fascicularis).Two intraperitoneal injections at a dose of 3.5 mL/kg,administered at weeks 1 and 23,recapitulated SLE features,including:production of antinuclear autoantibodies(ANA),membranoproliferative glomerulonephritis with immune complex(IC)deposition in the glomeruli.However,from week 27 five of eight pristanetreated monkeys developed progressive respiratory failure.Two of these died at week 28 and the remaining were euthanized at week 32.The histology of the monkey lungs suggested exogenous lipoid pneumonia.Thus,while pristane induced serological autoimmunity and characteristic renal manifestations in Macaca fascicularis,the consequent lipoid pneumonia limited the observation period and prevented comprehensive evaluation of SLE manifestations beyond 32 weeks.展开更多
Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in ...Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.展开更多
Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disord...Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disorder-related optic neuritis is the interaction of aquaporin-4 antibodies with the aquaporin-4 protein present on astrocytes within posterior optic nerve.This binding subsequently initiates a cascade of events leading to secondary demyelination of the optic nerve,ultimately culminating in optic nerve degeneration.Earlier studies on this disorder primarily used systemic-induced animal models,which often require prior activation of a systemic immune response.This can result in primary demyelination of the optic nerve,complicating the interpretation of experimental results.Such methodologies hinder the ability to isolate immune responses triggered by specific antibodies.Additionally,the lack of a detailed profile of disease progression over time limits our capacity to identify potential intervention windows.Therefore,constructing a targeted optic neuritis animal model induced by specific antibodies and elucidate the disease progression arecrucial for exploring the mechanisms underlying neuromyelitis optica spectrum disorder-related optic neuritis.In this study,specific antibodies against aquaporin-4 were precisely injected into the retrobulbar optic nerve of mice to induce a targeted inflammatory response in the posterior optic nerve,resulting in a more representative mouse model of neuromyelitis optica spectrum disorder-related optic neuritis than current models.The progression of the disease was then dynamically observed from both histological and functional perspectives over the course of 1 month following the induction of inflammation.By the first week,astrocytes were damaged,as evidenced by the loss of aquaporin-4 and glial fibrillary acidic protein,the activation of microglia,and the upregulation of microglia-related cytokines,including tumor necrosis factor,interleukin-6,interleukin-1β,C-X-C motif ligand 10,and brain-derived neurotrophic factor.Starting from the second week,there were signs of optic nerve demyelination and significant damage to axonal fibers and retinal ganglion cell bodies.Visual-evoked potentials and dark adaptation threshold responses in electroretinogram both indicated dysfunction in the visual pathway and retina,while optical coherence tomography revealed thinning of the retinal nerve fiber layer in live mice.In summary,in this study we conducted a dynamic exploration of the occurrence and progression of neuromyelitis optica spectrum disorder-related optic neuritis triggered by specific antibodies.Our results show pathological changes at various stages and correlate histological and molecular alterations with in vivo structural and functional deterioration.The findings from this study lay an important foundation for further research on neuromyelitis optica spectrum disorder-related optic neuritis.展开更多
Depressive disorder is a chronic,recurring,and potentially life-endangering neuropsychiatric disease.According to a report by the World Health Organization,the global population suffering from depression is experienci...Depressive disorder is a chronic,recurring,and potentially life-endangering neuropsychiatric disease.According to a report by the World Health Organization,the global population suffering from depression is experiencing a significant annual increase.Despite its prevalence and considerable impact on people,little is known about its pathogenesis.One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression.Furthermore,the neural circuit mechanism of depression induced by various factors is particularly complex.Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression,a comparison between the neural circuits of depression induced by various factors is essential for its treatment.In this review,we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression,aiming to provide a theoretical basis for depression prevention.展开更多
Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and n...Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and neural tissues,thereby signifi-cantly impacting the health of both humans and animals.Animal models are crucial for studying virus pathogenesis,vaccine development,and drug testing.Despite several vaccine candidates being in preclinical and clinical stages,no vaccines are current available to prevent lifelong infections caused by these human herpesviruses,except for varicella-zoster virus(VZV)vaccine.However,the strict host tropism of herpes-viruses and other limitations mean that no single animal model can fully replicate all key features of human herpesvirus-associated diseases.This makes it challeng-ing to evaluate vaccines and antivirals against human herpesvirus comprehensively.Herein,we summarize the current animal models used to study the human herpesvi-ruses includingα-herpesviruses(herpes simplex virus type 1(HSV-1),HSV-2,VZV),β-herpesviruses(human cytomegalovirus(HCMV),γ-herpesviruses(Epstein-Barr virus(EBV))and Kaposi's sarcoma herpesvirus(KSHV)).By providing concise information and detailed analysis of the potential,limitations and applications of various models,such as non-human primates,mice,rabbits,guinea pigs,and tree shrews,this sum-mary aims to help researchers efficiently select the most appropriate animal model,offering practical guidance for studying human herpesvirus.展开更多
Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to mode...Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to models of supratentorial ventricular hemorrhage,and there are no specific models of fourth ventricle hemorrhage.This limitation hinders comprehensive basic research and the understanding of the pathophysiological changes that occur following fourth ventricle hemorrhage.Therefore,the development of an animal model of fourth ventricle hemorrhage is highly important.Methods:In this study,a novel rat model of fourth ventricle hemorrhage was established via autologous blood injection through the foramen of Magendie.Anesthetized rats were positioned in a stereotaxic apparatus with their heads tilted downward at an angle of approximately 20°relative to the vertical axis.A needle was inserted through the foramen,and autologous blood obtained from the rat's heart was injected into the fourth ventricle via a microinfusion pump.Systematic evaluations of the model were conducted using small-animal magnetic resonance imaging,histopathological analysis,and neurological function assessment.Results:The rats developed stable and reproducible fourth ventricle hematomas and ventricular dilation.They also exhibited acute-phase hydrocephalus and pathological features of perilesional brain tissue injury,with observed neurological deficits comparable to patients with fourth ventricle hemorrhage.Conclusion:This model successfully recapitulates the clinicopathological and pathophysiological characteristics of patients with fourth ventricle hemorrhage and can be utilized for further investigation into the pathophysiological mechanisms underlying posthemorrhagic hydrocephalus and perilesional brainstem tissue injury.展开更多
BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spi...BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.展开更多
Background:Due to the widespread use of cell phone devices today,numerous re-search studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems.In most...Background:Due to the widespread use of cell phone devices today,numerous re-search studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems.In most studies,oxidative stress has been identified as the primary pathophysiological mechanism underlying the harmful effects of electromagnetic waves.This paper aims to provide a holistic review of the protective effects of melatonin against cell phone-induced electromag-netic waves on various organs.Methods:This study is a systematic review of articles chosen by searching Google Scholar,PubMed,Embase,Scopus,Web of Science,and Science Direct using the key-words‘melatonin’,‘cell phone radiation’,and‘animal model’.The search focused on articles written in English,which were reviewed and evaluated.The PRISMA process was used to review the articles chosen for the study,and the JBI checklist was used to check the quality of the reviewed articles.Results:In the final review of 11 valid quality-checked articles,the effects of me-latonin in the intervention group,the effects of electromagnetic waves in the case group,and the amount of melatonin in the chosen organ,i.e.brain,skin,eyes,testis and the kidney were thoroughly examined.The review showed that electromagnetic waves increase cellular anti-oxidative activity in different tissues such as the brain,the skin,the eyes,the testis,and the kidneys.Melatonin can considerably augment the anti-oxidative system of cells and protect tissues;these measurements were sig-nificantly increased in control groups.Electromagnetic waves can induce tissue atro-phy and cell death in various organs including the brain and the skin and this effect was highly decreased by melatonin.Conclusion:Our review confirms that melatonin effectively protects the organs of an-imal models against electromagnetic waves.In light of this conclusion and the current world-wide use of melatonin,future studies should advance to the stages of human clinical trials.We also recommend that more research in the field of melatonin physi-ology is conducted in order to protect exposed cells from dying and that melatonin should be considered as a pharmaceutical option for treating the complications result-ing from electromagnetic waves in humans.展开更多
Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the inju...Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.展开更多
Despite the well-established functions of neurotransmitters and their receptors in depression studies,the aetiology of depression remains unknown.Further research into the field of animal studies is required in order ...Despite the well-established functions of neurotransmitters and their receptors in depression studies,the aetiology of depression remains unknown.Further research into the field of animal studies is required in order to facilitate a more comprehensive understanding of the underlying mechanisms that contribute to the development of depression.While the potential of animal behaviour to elucidate the molecular underpinnings of depression remains to be elucidated,the establishment of animal models can facilitate the identification of analogous pathogenic pathways through the application of rigorous methodologies.Animal models that are suitable for simulating the illness state of human depression can be utilised to investigate the pathophysiology of depression and the development of novel antidepressant medications.Currently,there is an absence of an optimal animal model that can fully replicate the pathogenic pathways of human depression,which limits future research in this field.It is evident that stress constitutes the primary catalyst for the onset of depressive states,a phenomenon that has been observed in both human and animal subjects.From this standpoint,animal models of stress-induced depression should be better equipped to simulate the onset process of human depression.This study offers a comprehensive summary and analysis of the most frequently employed rodent models of depression,with a view to providing a more diverse range of models and resources for animal studies in the field of depression research.展开更多
Background:Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation(ECC).To evaluate the hemodynamic impact of ECC on atheromatous plaques,an atherosclerosis animal model,which is a...Background:Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation(ECC).To evaluate the hemodynamic impact of ECC on atheromatous plaques,an atherosclerosis animal model,which is also eligible for ECC,is required.Methods:Twenty-nine New Zealand White rabbits received a pro-atherosclerotic diet(group diet,n=10),a pro-atherosclerotic diet and additional intraaortic balloon insufflation injury(group BI,n=9),or served as controls(n=10).After 3 or 6 months,aortic explants were analyzed by(immuno-)histology and RT-PCR.Results:Blood serum analyses revealed increased cholesterol-levels in groups diet and BI compared to controls(3 months:p=0.03 each,6 months:p<0.0001 each).Aortic inflammatory infiltration was significantly enhanced in groups diet(CD3 at 3 months:p<0.0001,6 months:p=0.02;CD68 at 3 months:p=0.01)and BI(CD3 at 3 months:p<0.0001,6 months:p=0.03;CD68 at 3 months:p=0.04,6 months:p=0.02).Increased intima hyperplasia occurred in both groups(p<0.0001 each).Macroscopic analyses after 3 and 6 months showed ubiquitous lumen-narrowing aortic plaques.Calcification of the intima and media was increased in groups diet(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.01)and BI(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.02).Extensive lipid accumulation was found in the intima in both treatment groups(p<0.0001 each).Conclusions:A rabbit model with high aortic calcific plaque burden—diet-induced with no implicit need of an additional intimal injury by an intraaortic balloon insufflation due to comparable outcome—exhibiting multiple pathophysiological aspects of human atherosclerosis has been designed and thoroughly characterized.It is suitable for use in future studies on the interaction between atherosclerotic plaques and the arterial blood flow under ECC.展开更多
基金Ministry of Research,Innovation and Digitization,CCCDI-UEFISCDI,Grant/Award Number:PN-IV-P7-7.1-PED-2024-1578,within PNCDI Ⅳ.
文摘Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.
文摘Neurodegenerative diseases are increasing in prevalence due largely to aging populations worldwide and improved medical care for the elderly.Currently approved drugs can reduce some of the symptoms of neurodegenerative diseases but cannot cure them.Inflammation is involved in the development and progression of neurodegenerative diseases,and oxidative stress is implicated in neurodegeneration associated with cognitive decline and age-related cognitive impairment.Polyphenols such as curcumin,quercetin,and resveratrol possess potent anti-inflammatory and antioxidant properties.Nanoformulations of curcumin and quercetin can optimize their pharmacological effects in the treatment of neurodegenerative diseases.Nanocarriers play a crucial role in delivering drugs across the blood-brain barrier,thereby lowering the risk of peripheral side effects.Various nanoforms have been developed to induce bioavailability and solubility of curcumin and quercetin,including nanoparticles and nanoemulsions.The studies reviewed included 17 using curcumin nanoformulations and seven with quercetin nanoformulations and were tested in widely used animal models of Alzheimer’s disease,Parkinson’s disease,Huntington’s disease,and multiple sclerosis.Many of the curcumin and quercetin nanoformulations brought about improvements in learning and memory in behavioral tests of Alzheimer’s disease models and were effective in reducing oxidative stress in the brain.Both nanocurcumin and nanoquercetin decreased the levels of inflammatory markers in the brain.Nanocurcumin formulations improved motor behavior,gait,and memory in Parkinson’s disease models and increased dopaminergic neurons in the striatum and substantia nigra.Furthermore,nanocurcumin improved locomotor activity,memory,and learning,and the number of dendrites of medium spiny neurons in Huntington’s disease models.Nanocurcumin formulations decreased oxidative stress and inflammation in a model of demyelination.Several important limitations were identified in the studies reviewed and these need to be considered in future studies.Also,clinical trials could be performed using the currently available nanoforms of curcumin and quercetin.
基金National Natural Science Foundation of China,Grant/Award Number:32271496China Fundamental Research Funds for the Central Universities(Bejing Sport University)Grant/Award Number:2024TZJK001。
文摘Background:This study aims to explore the establishment of an animal model of car-diac injury induced by trimethylamine-N-oxide(TMAO),a metabolite secreted by gut microorganisms,and to investigate its application in moderate-intensity continuous training(MICT)intervention.Methods:C57BL6/J mice were randomly divided into four groups:normal mice(Nor,n=15);mice administered TMAO(TMAO,n=15);mice undergoing(Nor+MICT,n=15);mice undergoing(MICT)and administered TMAO(TMAO+MICT,n=15).Mice in the TMAO and TMAO+MICT groups received daily gavage of high-dose TMAO for 8 weeks,whereas those in the Nor+MICT and TMAO+MICT groups underwent MICT for 8 weeks(60 min per session,5 days per week,at 50%maximal running capacity).Cardiac function was evaluated using ultrasound,myocardial histology was examined using hematoxylin and eosin(HE)staining,and nuclear magnetic resonance(NMR)-based metabolomics was employed for multivariate statistical and metabolic pathway analyses.Results:Relative to the Nor group,TMAO-treated mice exhibited significant weight loss,elevated heart rate,and reduced ejection fraction and left ventricular fractional shortening,indicating cardiac impairment.Importantly,the TMAO+MICT group dem-onstrated significant improvements in these parameters compared to the TMAO group,alongside distinct alterations in myocardial metabolic profiles.TMAO altered five metabolic pathways relative to controls,whereas MICT induced significant changes in three pathways in TMAO-treated mice.Conclusion:Eight weeks of high-dose TMAO administration induced significant cardiac dysfunction in mice,which was effectively mitigated by MICT intervention.Consequently,this animal model serves as a valuable tool for investigating the mecha-nisms underlying the impact of MICT on cardiovascular diseases.
基金The Youth Project of Tianjin Natural Science Foundation,Grant/Award Number:23JCQNJC01380。
文摘Background:The traditional method of heterotopic abdominal heart transplantation(HTx)involves crossclamping the inferior vena cava,which inevitably leads to bilateral lower limb ischemia(LI).This study first aimed to investigate the impact of LI on renal function in rats subjected to unilateral nephrectomy(UNx).Second,a modified method utilizing renal vessel-assisted anastomosis in rats with left UNx was compared with the traditional method for abdominal HTx.Methods:Male Sprague-Dawley rats were utilized as subjects for both experimental phases.In experiment 1,the animals were divided into four groups:sham operation group;LI group-rats undergoing occlusion of the abdominal aorta and vena cava below the renal vessels;UNx group-rats with left UNx;and LI+UNx group.All operated animals were monitored for up to 7 days for biochemical markers,renal histopathology,and survival rates.In experiment 2,we introduced the renal vessel-assisted method as the experimental group and compared it against the traditional method as the control within rat heterotopic HTx models.We assessed operative characteristics,echocardiography results,histological findings,and graft survival.Results:First,LI resulted in acute kidney dysfunction characterized by a decrease in 7day survival rates and creatinine clearance rates in both the LI and LI+UNx groups compared to the sham operation and UNx groups.Particularly,histopathological damage in the kidney and liver did not exhibit significant effects during this period.Second,the implementation of the renal vessel-assisted method significantly reduced bleeding volume at suture sites and enhanced the 7day survival rate compared to the traditional method.Conclusion:Acute kidney injury was induced by LI postoperation in treated rats.The renal vessel-assisted method demonstrated its effectiveness as a superior alternative that mitigates complications associated with the traditional method.
基金supported by the Hartman Behavioral Neuroscience Laboratory.
文摘Background:Healthy non-pharmacological lifestyle factors,such as regular physical exercise and dietary supplementation,have been shown to significantly improve cognitive outcomes over time compared to a more sedentary lifestyle and poor diet.Furthermore,exercise may serve as a potential protective factor in attenuating the effects associated with cognitive decline that are characteristic of neurodegenerative disorders,such as Alzheimer's disease(AD).Evidence indicates that certain dietary interventions can also attenuate the effects of neurodegeneration and positively impact longevity.Supplementation with polyphenols such as ellagic acid(EA),which is abundant in pomegranate juice,may help provide neuroprotective and longevity benefits.Methods:This study examined the potential protective potential of EA and exercise and provides insight into the combined use of a polyphenol-rich diet and exercise to enhance behavioral outcomes and lifespan in a transgenic Drosophila melanogaster(fruit fly)model of AD with the Aβ_(42) gene.Results:Fruit flies subjected to a 120-minute exercise regimen performed better on a climbing assay than flies that did not exercise.Conversely,flies that exercised for 30 min passed marginally more trials on a learning and memory assay using an aversive stimulus than flies that did not exercise,whereas both groups performed better than flies subjected to the more intense exercise condition.Conclusion:These results suggest a hormetic effect of exercise regarding memory performance.Finally,flies fed a low dose of dietary EA(0.24 mg/mL)lived significantly longer than flies fed the control diet or higher concentrations of EA,again suggesting a hormetic effect of EA on longevity.
基金Supported by the National Key Specialty of Traditional Chinese Medicine(Spleen and Stomach Diseases),No.0500004National Natural Science Foundation of China,No.82205104 and No.82104850+1 种基金Hospital Capability Enhancement Project of Xiyuan Hospital,CACMS,No.XYZX0303-07the Fundamental Research Funds for the Central Public Welfare Research Institutes,Excellent Young Scientists Training Program of China Academy of Chinese Medical Sciences,No.ZZ16-YQ-002.
文摘BACKGROUND Non-erosive reflux disease(NERD),the main gastroesophageal reflux subtype,features reflux symptoms without mucosal damage.Anxiety links to visceral hypersensitivity in NERD,yet mechanisms and animal models are unclear.AIM To establish a translational NERD rat model with anxiety comorbidity via tail clamping and study corticotropin-releasing hormone(CRH)-mediated neuroimmune pathways in visceral hypersensitivity and esophageal injury.METHODS Sprague-Dawley(SD)and Wistar rats were grouped into sham,model,and modified groups(n=10 each).The treatments for the modified groups were as follows:SD rats received ovalbumin/aluminum hydroxide suspension+acid perfusion±tail clamping(40 minutes/day for 7 days),while Wistar rats received fructose water+tail clamping.Esophageal pathology,visceral sensitivity,and behavior were assessed.Serum CRH,calcitonin gene-related peptide(CGRP),5-hydroxytryptamine(5-HT),and mast cell tryptase(MCT)and central amygdala(CeA)CRH mRNA were measured via ELISA and qRT-PCR.RESULTS Tail clamping induced anxiety,worsening visceral hypersensitivity(lower abdominal withdrawal reflex thresholds,P<0.05)and esophageal injury(dilated intercellular spaces and mitochondrial edema).Both models showed raised serum CRH,CGRP,5-HT,and MCT(P<0.01)and CeA CRH mRNA expression(P<0.01).Behavioral tests confirmed anxiety-like phenotypes.NERD-anxiety rats showed clinical-like symptom severity without erosion.CONCLUSION Tail clamping induces anxiety in NERD models,worsening visceral hypersensitivity via CRH neuroimmune dysregulation,offering a translational model and highlighting CRH as a treatment target.
基金National Natural Science Foundation of China,Grant/Award Number:82000102 and 82270112。
文摘The incidence of benign airway stenosis(BAS)is on the rise,and current treatment options are associated with a significant risk of restenosis.Therefore,there is an urgent need to explore new and effective prevention and treatment methods.Animal models serve as essential tools for investigating disease mechanisms and assessing novel therapeutic strategies,and the scientific rigor of their construction and validation significantly impacts the reliability of research findings.This paper systematically reviews the research progress and evaluation systems of BAS animal models over the past decade,aiming to provide a robust foundation for the optimized construction of BAS models,intervention studies,and clinical translation.This effort is intended to facilitate the innovation and advancement in BAS prevention and treatment strategies.
文摘Background:In preclinical research,tumor growth inhibition in subcutaneous models is frequently employed to evaluate therapeutic efficacy;however,such models often lack clinical translatability.Methods:To better approximate clinical reality,taking the case of doxorubicin treatment,we utilized an orthotopic transplant and resection(OtR)strategy to systematically assess the effects of neoadjuvant chemotherapy,adjuvant chem-otherapy,and their combination on tumor growth,recurrence,and malignant progression.Results:Surprisingly,none of the treatments improved mouse survival,with adjuvant therapy even shortening it.Although neoadjuvant chemotherapy delayed preopera-tive tumor growth,and all regimens reduced recurrence rates,none effectively pre-vented metastasis.Furthermore,all treatment groups exhibited weight loss,indicative of chemotherapy-induced cachexia.Conclusions:Collectively,these findings demonstrate that reduced tumor growth in preclinical mouse models does not necessarily translate into overall survival benefit.Our results emphasize the critical importance of prioritizing metastasis prevention over tumor growth inhibition as a key efficacy endpoint in antitumor drug evaluation.
基金supported by the National Key Research and Development Program,China(2022YFC3502103,2022YFC3502102)the National Natural Science Foundation of China,China(82204751).
文摘This study summarizes the theoretical basis,modeling strategies,pathological mechanisms,and therapeutic advances related to high-altitude qi-deficiency and blood-stasis pattern.Traditional concepts such as“qi drives blood”and“deficiency leads to stasis”closely align with modern evidence demonstrating that hypoxia disrupts energy metabolism,impairs microcirculation,and amplifies inflammation and oxidative stress.Current animal models commonly use hypobaric hypoxia combined with fatigue loading,dietary restriction,ice-water stimulation,or adrenaline injection to mimic the combined effects of qi deficiency,blood stasis,and hypoxic injury.These composite approaches reproduce systemic abnormalities,including reduced arterial oxygen partial pressure,increased blood viscosity,impaired cardiac and pulmonary function,microcirculatory obstruction,and mitochondrial dysfunction.Enhanced inflammatory signaling,oxidative stress,and disturbances in metabolic and epigenetic networks further characterize the pattern.The findings indicate that its pathogenesis arises from multi-system,multi-target interactions rather than a single pathway.Representative herbal formulas,such as Buyang Huanwu decoction,Xuefu Zhuyu decoction,and prescriptions rich in Astragalus membranaceus(Fisch.)Bunge(A.membranaceus,Huang qi)or Salvia miltiorrhiza Bunge(S.miltiorrhiza,Dan Shen)have demonstrated the ability to improve energy metabolism,attenuate endothelial injury,enhance microcirculation,and suppress inflammation through network-level regulation.Future research should focus on standardizing exposure parameters,developing quantitative syndrome evaluation systems,and integrating multi-omics,systems biology and artificial intelligence to improve model reproducibility and mechanistic precision.These efforts may help establish objective criteria for high-altitude qi-deficiency and blood-stasis pattern and support the development of targeted therapeutic strategies.
文摘A lupuslike condition induced by intraperitoneal administration of pristane(2,6,10,14 tetramethylpentadecane)in mice is widely used as a model of systemic lupus erythematosus(SLE).Due to their phylogenetic distance from humans,murine models are not always suitable tool for studying the specific activity of therapeutic agents and the pathogenesis of SLE.In order to overcome speciesspecific limitations of murine models,this approach was tested in nonhuman primates-cynomolgus monkeys(Macaca fascicularis).Two intraperitoneal injections at a dose of 3.5 mL/kg,administered at weeks 1 and 23,recapitulated SLE features,including:production of antinuclear autoantibodies(ANA),membranoproliferative glomerulonephritis with immune complex(IC)deposition in the glomeruli.However,from week 27 five of eight pristanetreated monkeys developed progressive respiratory failure.Two of these died at week 28 and the remaining were euthanized at week 32.The histology of the monkey lungs suggested exogenous lipoid pneumonia.Thus,while pristane induced serological autoimmunity and characteristic renal manifestations in Macaca fascicularis,the consequent lipoid pneumonia limited the observation period and prevented comprehensive evaluation of SLE manifestations beyond 32 weeks.
文摘Myasthenia gravis is a chronic autoimmune disorder that affects the neuromuscular junction leading to fluctuating skeletal muscle fatigability. The majority of myasthenia gravis patients have detectable antibodies in their serum, targeting acetylcholine receptor, muscle-specific kinase, or related proteins. Current treatment for myasthenia gravis involves symptomatic therapy, immunosuppressive drugs such as corticosteroids, azathioprine, and mycophenolate mofetil, and thymectomy, which is primarily indicated in patients with thymoma or thymic hyperplasia. However, this condition continues to pose significant challenges including an unpredictable and variable disease progression, differing response to individual therapies, and substantial longterm side effects associated with standard treatments(including an increased risk of infections, osteoporosis, and diabetes), underscoring the necessity for a more personalized approach to treatment. Furthermore, about fifteen percent of patients, called “refractory myasthenia gravis patients”, do not respond adequately to standard therapies. In this context, the introduction of molecular therapies has marked a significant advance in myasthenia gravis management. Advances in understanding myasthenia gravis pathogenesis, especially the role of pathogenic antibodies, have driven the development of these biological drugs, which offer more selective, rapid, and safer alternatives to traditional immunosuppressants. This review aims to provide a comprehensive overview of emerging therapeutic strategies targeting specific immune pathways in myasthenia gravis, with a particular focus on preclinical evidence, therapeutic rationale, and clinical translation of B-cell depletion therapies, neonatal Fc receptor inhibitors, and complement inhibitors.
基金The study was partially supported by the General Research Fund(GRF)from the Research Grants Council(RGC)of the Hong Kong Special Administrative Region,China,No.15103522(to ST)the Internal Research Grant from the Hong Kong Polytechnic University 2021-23,No.P0035512(to ST)and P0035375(to HHLC)+1 种基金the Innovation and Technology Commission of the Hong Kong Special Administrative Region(ITC InnoHK CEVR Project)The Hong Kong Polytechnics University Research Center for Sharp Vision,No.P0039595.
文摘Neuromyelitis optica spectrum disorder-related optic neuritis involves various cellular responses to inflammation and degeneration.In most patients,the primary mechanism underlying neuromyelitis optica spectrum disorder-related optic neuritis is the interaction of aquaporin-4 antibodies with the aquaporin-4 protein present on astrocytes within posterior optic nerve.This binding subsequently initiates a cascade of events leading to secondary demyelination of the optic nerve,ultimately culminating in optic nerve degeneration.Earlier studies on this disorder primarily used systemic-induced animal models,which often require prior activation of a systemic immune response.This can result in primary demyelination of the optic nerve,complicating the interpretation of experimental results.Such methodologies hinder the ability to isolate immune responses triggered by specific antibodies.Additionally,the lack of a detailed profile of disease progression over time limits our capacity to identify potential intervention windows.Therefore,constructing a targeted optic neuritis animal model induced by specific antibodies and elucidate the disease progression arecrucial for exploring the mechanisms underlying neuromyelitis optica spectrum disorder-related optic neuritis.In this study,specific antibodies against aquaporin-4 were precisely injected into the retrobulbar optic nerve of mice to induce a targeted inflammatory response in the posterior optic nerve,resulting in a more representative mouse model of neuromyelitis optica spectrum disorder-related optic neuritis than current models.The progression of the disease was then dynamically observed from both histological and functional perspectives over the course of 1 month following the induction of inflammation.By the first week,astrocytes were damaged,as evidenced by the loss of aquaporin-4 and glial fibrillary acidic protein,the activation of microglia,and the upregulation of microglia-related cytokines,including tumor necrosis factor,interleukin-6,interleukin-1β,C-X-C motif ligand 10,and brain-derived neurotrophic factor.Starting from the second week,there were signs of optic nerve demyelination and significant damage to axonal fibers and retinal ganglion cell bodies.Visual-evoked potentials and dark adaptation threshold responses in electroretinogram both indicated dysfunction in the visual pathway and retina,while optical coherence tomography revealed thinning of the retinal nerve fiber layer in live mice.In summary,in this study we conducted a dynamic exploration of the occurrence and progression of neuromyelitis optica spectrum disorder-related optic neuritis triggered by specific antibodies.Our results show pathological changes at various stages and correlate histological and molecular alterations with in vivo structural and functional deterioration.The findings from this study lay an important foundation for further research on neuromyelitis optica spectrum disorder-related optic neuritis.
基金supported by the Brain&Behavior Research Foundation(30233).
文摘Depressive disorder is a chronic,recurring,and potentially life-endangering neuropsychiatric disease.According to a report by the World Health Organization,the global population suffering from depression is experiencing a significant annual increase.Despite its prevalence and considerable impact on people,little is known about its pathogenesis.One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression.Furthermore,the neural circuit mechanism of depression induced by various factors is particularly complex.Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression,a comparison between the neural circuits of depression induced by various factors is essential for its treatment.In this review,we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression,aiming to provide a theoretical basis for depression prevention.
基金National Natural Science Foundation of China,Grant/Award Number:82222041 and 82241068CAMS Innovation Fund for Medical Sciences,Grant/Award Number:2021-I2M-1-037 and 2023-I2M-2-001+1 种基金National Key Research and Development Project of China,Grant/Award Number:2023YFC2309000Beijing Natural Science Foundation,Grant/Award Number:Z220018。
文摘Human herpesvirus,a specific group within the herpesvirus family,is responsible for a variety of human diseases.These viruses can infect humans and other vertebrates,primarily targeting the skin,mucous membranes,and neural tissues,thereby signifi-cantly impacting the health of both humans and animals.Animal models are crucial for studying virus pathogenesis,vaccine development,and drug testing.Despite several vaccine candidates being in preclinical and clinical stages,no vaccines are current available to prevent lifelong infections caused by these human herpesviruses,except for varicella-zoster virus(VZV)vaccine.However,the strict host tropism of herpes-viruses and other limitations mean that no single animal model can fully replicate all key features of human herpesvirus-associated diseases.This makes it challeng-ing to evaluate vaccines and antivirals against human herpesvirus comprehensively.Herein,we summarize the current animal models used to study the human herpesvi-ruses includingα-herpesviruses(herpes simplex virus type 1(HSV-1),HSV-2,VZV),β-herpesviruses(human cytomegalovirus(HCMV),γ-herpesviruses(Epstein-Barr virus(EBV))and Kaposi's sarcoma herpesvirus(KSHV)).By providing concise information and detailed analysis of the potential,limitations and applications of various models,such as non-human primates,mice,rabbits,guinea pigs,and tree shrews,this sum-mary aims to help researchers efficiently select the most appropriate animal model,offering practical guidance for studying human herpesvirus.
基金Natural Science Foundation of Hubei Province,Grant/Award Number:2024AFB877the Chongqing Medical Scientific Research Project(Joint Project of Chongqing Health Commission and Science&Technology Bureau),Grant/Award Number:2023GGXM003+3 种基金Chongqing Municipal Health Commission,Grant/Award Number:YXGD202451Organization Department of Chongqing Municipal Party Committee,Grant/Award Number:cstc2024ycjh-bgzxm0103National Natural Science Foundation of China,Grant/Award Number:82371361Jingmen Science and Technology Bureau,Grant/Award Number:2024ZDYF012。
文摘Background:Hemorrhagic expansion into the fourth ventricle is an independent risk factor for poor outcomes in intraventricular hemorrhage(IVH)patients.However,to date,available animal models of IVH are limited to models of supratentorial ventricular hemorrhage,and there are no specific models of fourth ventricle hemorrhage.This limitation hinders comprehensive basic research and the understanding of the pathophysiological changes that occur following fourth ventricle hemorrhage.Therefore,the development of an animal model of fourth ventricle hemorrhage is highly important.Methods:In this study,a novel rat model of fourth ventricle hemorrhage was established via autologous blood injection through the foramen of Magendie.Anesthetized rats were positioned in a stereotaxic apparatus with their heads tilted downward at an angle of approximately 20°relative to the vertical axis.A needle was inserted through the foramen,and autologous blood obtained from the rat's heart was injected into the fourth ventricle via a microinfusion pump.Systematic evaluations of the model were conducted using small-animal magnetic resonance imaging,histopathological analysis,and neurological function assessment.Results:The rats developed stable and reproducible fourth ventricle hematomas and ventricular dilation.They also exhibited acute-phase hydrocephalus and pathological features of perilesional brain tissue injury,with observed neurological deficits comparable to patients with fourth ventricle hemorrhage.Conclusion:This model successfully recapitulates the clinicopathological and pathophysiological characteristics of patients with fourth ventricle hemorrhage and can be utilized for further investigation into the pathophysiological mechanisms underlying posthemorrhagic hydrocephalus and perilesional brainstem tissue injury.
基金Supported by Lanzhou City Science and Technology Development Guiding Plan Project,No.2023-ZD-170Lanzhou Science and Technology Plan Project,No.2023-2-11High-Level Talent Training Project At the 940th Hospital of the Joint Logistics Force,No.2024-G3-5.
文摘BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.
基金Deputy for Research and Technology,Kermanshah University of Medical Sciences,Grant/Award Number:4030031。
文摘Background:Due to the widespread use of cell phone devices today,numerous re-search studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems.In most studies,oxidative stress has been identified as the primary pathophysiological mechanism underlying the harmful effects of electromagnetic waves.This paper aims to provide a holistic review of the protective effects of melatonin against cell phone-induced electromag-netic waves on various organs.Methods:This study is a systematic review of articles chosen by searching Google Scholar,PubMed,Embase,Scopus,Web of Science,and Science Direct using the key-words‘melatonin’,‘cell phone radiation’,and‘animal model’.The search focused on articles written in English,which were reviewed and evaluated.The PRISMA process was used to review the articles chosen for the study,and the JBI checklist was used to check the quality of the reviewed articles.Results:In the final review of 11 valid quality-checked articles,the effects of me-latonin in the intervention group,the effects of electromagnetic waves in the case group,and the amount of melatonin in the chosen organ,i.e.brain,skin,eyes,testis and the kidney were thoroughly examined.The review showed that electromagnetic waves increase cellular anti-oxidative activity in different tissues such as the brain,the skin,the eyes,the testis,and the kidneys.Melatonin can considerably augment the anti-oxidative system of cells and protect tissues;these measurements were sig-nificantly increased in control groups.Electromagnetic waves can induce tissue atro-phy and cell death in various organs including the brain and the skin and this effect was highly decreased by melatonin.Conclusion:Our review confirms that melatonin effectively protects the organs of an-imal models against electromagnetic waves.In light of this conclusion and the current world-wide use of melatonin,future studies should advance to the stages of human clinical trials.We also recommend that more research in the field of melatonin physi-ology is conducted in order to protect exposed cells from dying and that melatonin should be considered as a pharmaceutical option for treating the complications result-ing from electromagnetic waves in humans.
基金supported by the National Key Research and Development Program(2021YFC3002205)the Postgraduate Research and Innovation Program of Tianjin Municipal Education Commission(2022BKY113),China.
文摘Cardiac arrest(CA)is a critical condition in the field of cardiovascular medicine.Despite successful resuscitation,patients continue to have a high mortality rate,largely due to post CA syndrome(PCAS).However,the injury and pathophysiological mechanisms underlying PCAS remain unclear.Experimental animal models are valuable tools for exploring the etiology,pathogenesis,and potential interventions for CA and PCAS.Current CA animal models include electrical induction of ventricular fibrillation(VF),myocardial infarction,high potassium,asphyxia,and hemorrhagic shock.Although these models do not fully replicate the complexity of clinical CA,the mechanistic insights they provide remain highly relevant,including post-CA brain injury(PCABI),post-CA myocardial dysfunction(PAMD),systemic ischaemia/reperfusion injury(IRI),and the persistent precipitating pathology.Summarizing the methods of establishing CA models,the challenges encountered in the modeling process,and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
文摘Despite the well-established functions of neurotransmitters and their receptors in depression studies,the aetiology of depression remains unknown.Further research into the field of animal studies is required in order to facilitate a more comprehensive understanding of the underlying mechanisms that contribute to the development of depression.While the potential of animal behaviour to elucidate the molecular underpinnings of depression remains to be elucidated,the establishment of animal models can facilitate the identification of analogous pathogenic pathways through the application of rigorous methodologies.Animal models that are suitable for simulating the illness state of human depression can be utilised to investigate the pathophysiology of depression and the development of novel antidepressant medications.Currently,there is an absence of an optimal animal model that can fully replicate the pathogenic pathways of human depression,which limits future research in this field.It is evident that stress constitutes the primary catalyst for the onset of depressive states,a phenomenon that has been observed in both human and animal subjects.From this standpoint,animal models of stress-induced depression should be better equipped to simulate the onset process of human depression.This study offers a comprehensive summary and analysis of the most frequently employed rodent models of depression,with a view to providing a more diverse range of models and resources for animal studies in the field of depression research.
基金German Heart Foundation/German Foundation of Heart Research。
文摘Background:Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation(ECC).To evaluate the hemodynamic impact of ECC on atheromatous plaques,an atherosclerosis animal model,which is also eligible for ECC,is required.Methods:Twenty-nine New Zealand White rabbits received a pro-atherosclerotic diet(group diet,n=10),a pro-atherosclerotic diet and additional intraaortic balloon insufflation injury(group BI,n=9),or served as controls(n=10).After 3 or 6 months,aortic explants were analyzed by(immuno-)histology and RT-PCR.Results:Blood serum analyses revealed increased cholesterol-levels in groups diet and BI compared to controls(3 months:p=0.03 each,6 months:p<0.0001 each).Aortic inflammatory infiltration was significantly enhanced in groups diet(CD3 at 3 months:p<0.0001,6 months:p=0.02;CD68 at 3 months:p=0.01)and BI(CD3 at 3 months:p<0.0001,6 months:p=0.03;CD68 at 3 months:p=0.04,6 months:p=0.02).Increased intima hyperplasia occurred in both groups(p<0.0001 each).Macroscopic analyses after 3 and 6 months showed ubiquitous lumen-narrowing aortic plaques.Calcification of the intima and media was increased in groups diet(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.01)and BI(intima:p<0.0001 at 3 and 6 months;media at 3 months:p<0.0001,6 months:p=0.02).Extensive lipid accumulation was found in the intima in both treatment groups(p<0.0001 each).Conclusions:A rabbit model with high aortic calcific plaque burden—diet-induced with no implicit need of an additional intimal injury by an intraaortic balloon insufflation due to comparable outcome—exhibiting multiple pathophysiological aspects of human atherosclerosis has been designed and thoroughly characterized.It is suitable for use in future studies on the interaction between atherosclerotic plaques and the arterial blood flow under ECC.
