Experimental animal models in traumatic brain injury research: a comprehensive review of methods and outlook

Traumatic brain injury (TBI) remains a significant public health concern worldwide, necessitating effective research models to elucidate its pathophysiology and develop therapeutic interventions. Animal models play a crucial role in TBI research, offering valuable insights into injury mechanisms and potential treatments. However, selecting the appropriate model can be challenging due to diverse array of available options and their respective advantages and limitations. In this comprehensive review, we examine four commonly used animal models of TBI: the weight drop, fluid percussion, cortical impact, and blast injury models. Each model is characterized by distinct injury mechanisms, allowing researchers simulate various aspects of TBI pathology. We discuss the unique advantages and disadvantages of each model, providing insights into their applications and considerations for model selection based on research objectives and outcome measures. Furthermore, we highlight emerging directions in TBI modelling, emphasizing the importance of refining and innovating models to replicate the complexity of human TBI. By critically evaluating and understanding the subtlety of different TBI models, researchers can make informed decisions to enhance the translational potential of preclinical TBI research and ultimately improve clinical outcomes for TBI patients.

Progress in study on animal models of trigeminal neuralgia / 中南大学学报(医学版)

Trigeminal neuralgia is a manifestation of orofacial neuropathic pain disorder,always deemed to be an insurmountable peak in the field of pain research and treatment.The pain is recurrent,abrupt in onset and termination similar to an electric shock or described as shooting.A poor quality of life has been attributed to trigeminal neuralgia,as the paroxysms of pain may be triggered by innocuous stimuli on the face or inside the oral cavity,such as talking,washing face,chewing and brushing teeth in daily life.The pathogenesis of trigeminal neuralgia has not been fully elucidated,although the microvascular compression in the trigeminal root entry zone is generally considered to be involved in the emergence and progression of the pain disorder.In addition,orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve might be secondary to peripheral nerve injury.Based on current hypotheses regarding the potential causes,a variety of animal models have been designed to simulate the pathogenesis of trigeminal neuralgia,including models of compression applied to the trigeminal nerve root or trigeminal ganglion,chronic peripheral nerve injury,peripheral inflammatory pain and center-induced pain.However,it has not yet been possible to determine which model can be perfectly employed to explain the mechanisms.The selection of appropriate animal models is of great significance for the study of trigeminal neuralgia.Therefore,it is necessary to discuss the characteristics of the animal models in terms of animal strains,materials,operation methods and behavior observation,in order to gain insight into the research progress in animal models of trigeminal neuralgia.In the future,animal models that closely resemble the features of human trigeminal neuralgia pathogenesis need to be developed,with the aim of making valuable contributions to the relevant basic and translational medical research.

Guidelines for the Selection of Animal Models and Preclinical Drug Trials for Spontaneous Intracerebral Hemorrhage (2024 Edition) / 实验动物与比较医学

Spontaneous intracerebral hemorrhage (sICH), the most prevalent and lethal subtype of stroke, is characterized by spontaneous hemorrhage in the brain parenchyma. Presently, there are no effective methods for preventing and treating sICH. The existing sICH animal models can be broadly categorized into three classes: (1) induced intracerebral hemorrhage models, including autologous blood injection model, collagenase injection model, microballoon inflation model, and hyperglycemia-induced sICH hematoma expansion model; (2) spontaneous hypertensive intracerebral hemorrhage models mainly include stroke-prone spontaneously hypertensive rats (SHRsp) and stroke-prone renovascular hypertensive rats (RHRsp); (3) gene-modified models encompassing transgentic hypertensive intracerebral hemorrhage, transgentic cerebral amyloid angiopathy, arteriovenous malformation-related, cerebral cavernous malformation-related and collagen-related genetically modified animal models for sICH. These models contribute not only to unraveling the pathogenesis of sICH and exploring preventive or therapeutic interventions, but also serve as invaluable tools for conducting preclinical drug trials to advance novel treatments. This guide comprehensively reviews sICH pathogenesis, delineates the superiority and inferiority of different species of modeling animals, explains the modeling principles and techniques for various sICH animal models, elucidates the technical details of animal model production, summarizes the pathophysiological mechanism simulated by the models and their clinical relevance, outlines the neurobehavioral evaluation methodologies for sICH animal models, compares the advantages and disadvantages of various models, and suggests their applicable research areas. Additionally, it underscores critical considerations in the design of preclinical drug trials for sICH.

Mechanism of calcium oxalate kidney stone formation mediated by autophagy and endoplasmic reticulum stress pathway regulated by p38 MAPK pathway / 现代泌尿外科杂志

【Objective】 To explore the effects and mechanism of p38 mitogen activated protein kinase (MAPK) pathway on the formation of calcium oxalate (CaOx) kidney stones in rats,so as to provide new ideas for the treatment of kidney stones. 【Methods】 A total of 40 rats were divided into control, SB203580, CaOx and SB203580+CaOx groups, with 10 rats in each group.Intragastric administration of a mixture of 1% ethylene glycol and 1% ammonium chloride was given to the CaOx and SB203580+CaOx groups to construct CaOx models, while intragastric administration of drinking water was given to the control and SB203580 groups.After molding, SB203580 and SB203580+CaOx groups were injected with 5 mg/kg SB203580 peritoneally once a day for 14 days, while the control and CaOx groups were injected with equal volume of normal saline.The renal mass of rats was measured and the renal coefficient was calculated; the serum levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were measured with an automated biochemical analyzer; the urinary levels of neutrophil gelatinase-associated lipid carrier protein (NGAL) and kidney injury molecule-1 (KIM-1) were determined with enzyme-linked immunosorbent assay (ELISA); the crystal deposition and tissue damage in renal tissues were observed with Von Kossa staining; the apoptosis of renal tubule cells was observed with TUNEL; the expressions of autophagy markers in kidney tissues were detected with immunohistochemical staining; the molecular expressions of autophagy-endoplasmic reticulum stress related pathways in renal tissues were determined with RT-qPCR and Western blot. 【Results】 Compared with the CaOx group, the SB203580+CaOx group had increased body mass after molding (P<0.05); decreased kidney mass, kidney coefficient, BUN, SCr, NGAL and KIM-1 levels (P<0.05); alleviated pathological damage of kidney tissues; significantly reduced black crystal; down-regulated proportion of positive TUNEL cells, positive expression area of LC3B and Beclin-1, mRNA expressions of LC3B, Beclin-1, CHOP and GRP78, protein ratio of LC3-Ⅱ/LC3-Ⅰ, and protein expressions of Beclin-1, CHOP and GRP78 (P<0.05); but up-regulated mRNA and protein expressions of p62 (P<0.05). 【Conclusion】 The p38 MAPK pathway is involved in the formation of CaOx kidney stones in rats.Inhibition of this pathway can reduce the formation of kidney stones, which may be related to the regulation of autophagy and endoplasmic reticulum stress.

Research progress on bone metabolism and molecular mechanisms in accelerated aging SAMP6 mice / 中国药理学通报

Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. The pathogenesis of SOP is complex and not well understood. Currently, the rapid aging model mouse, senescence accelerated mouse prone 6 (SAMP6), is an ideal model for studying the mechanisms of SOP development and exploring its prevention and treatment. This model exhibits characteristics including increased bone fragility, degradation of bone microstructure, loss of bone matrix, and abnormal metabolism and dysfunction of bone cells, faithfully replicating the process of SOP occurrence and progression at both macroscopic and microscopic levels.

Ethical and Welfare Review in the Modeling Process of Disease Animal Models / 医用生物力学

Disease animal model is an indispensable part of studying the pathogenesis and treatment of diseases.Review of the ethics and welfare is the necessary measure to ensure the quality of scientific research and promote the scientific and rational use of laboratory animals.In the review practice,it is found that most applicants are difficult to accurately understand the items listed in the application form and ethical principles related to items.Therefore,a practical and feasible set of ethical guidelines for animal experiments is necessary.This review focuses on the legal and ethical basis of developing oral disease animal models,and divides the methods of establishing oral disease animal models into physical methods,chemical methods,biological methods,and combined methods.It also elaborates on the ethical and welfare review points of different modeling methods and model evaluation methods.Hopefully,ethical censors and project applicants may get more understanding of ethical review for disease animal models,and ultimately improve the standardization and applicability of animal models.

Analysis of animal models of vertigo based on the characteristics of clinical conditions in Chinese and Western medicines / 中国实验动物学报

Objective To classify and analyze the existing animal models of vertigo based on the clinical characteristics of Chinese and Western medicines,evaluate the clinical fit of the models,and their advantages and disadvantages,to improve the existing animal models and provide a more intuitive reference for clinical research.Methods The existing animal models of vertigo in the database from January 2000 to March 2023 were searched,and the models were classified by the modeling method combined with the characteristics of Chinese and Western medicine clinical conditions of vertigo and the existing animal model evaluation method,and assigned values to evaluate the clinical fit and the advantages and disadvantages of the models.Results The existing animal models of vertigo were neck surgery,motor stimulation,otogenic stimulation,sclerotherapy injection,flight variation pressure,vertebral artery ligation,and stasis injection models.Among them,the Western medical fit was high for the neck surgery model(65％)and otogenic stimulation model(65％).All models had a moderate Chinese medical fit(50％≤fit＜60％)or low(fit＜50％)TCM anast omosis.No model had both high Chinese and Western medicines anastomosis.Conclusions The animal models of vertigo are mainly Western medicine disease models,Chinese medicine evidence models are lacking,and few models have a high clinical fit between Chinese and Western medicines,which fail to highlight the characteristics of Chinese medicine.Therefore,the establishment of animal models of vertigo that are closely integrated with the clinical characteristics of Chinese and Western medicines may provide more reasonable and comprehensive experimental support for the development,screening,and clinical evaluation of new anti-vertigo drugs.

Establishment and analysis of NLRP3-/- mouse models of ulcerative colitis / 中国实验动物学报

Objective To induce an NLRP3-/- mouse model of ulcerative colitis(UC)using different concentrations of dextran sulfate sodium(DSS)and different administration times,and to analyze and evaluate the advantages and disadvantages of the preparations to provide a more suitable animal model for the study of UC pathogenesis in humans and the development of therapeutic drugs.Methods Forty-eight male NLRP3-/- specific-pathogen-free mice were divided randomly into blank,2.5％7 d,3％7 d,and 3％5 d groups(n=12 mice per group).UC mouse models were induced using combinations of different concentrations and administration times of DSS.Body weight,DAI(disease activity index)score,hematoxylin and eosin(HE)staining,colon length,and related indicators(interleukin IL-6,tumor necrosis factor(TNF)-α,and tight junction protein(ZO-1))were observed and evaluated.Results(1)UC membrane type was induced in each group with different concentrations and administration times.(2)Mouse body weight decreased,the fecal occult blood became more positive,the DAI score increased,and more mice died with increasing DSS concentration and administration time.(3)Longer administration time and higher concentration of DSS were also associated with more severe damage to the intestinal mucosa,as shown by HE staining.(4)Immunohistochemistry showed that the inflammatory factors TNF-α and IL-6 were increased in the model group compared with the blank control group,while expression of ZO-1 was decreased compared with the blank group.Conclusions(1)Administration of 2.5％or 3％DSS for 7 days or 3％DSS for 5 days can induce UC in NLRP3-/- mice.(2)The combination of DAI score,HE staining,the detection of related indicators,and mouse survival rate indicated that NLRP3-/- mice treated with 3％DSS for 5 days produced the most suitable UC model to study the clinical manifestations and drug treatment of UC.

Research status and trend of depression models in animals:a bibliometric analysis based on CiteSpace / 中国比较医学杂志

Objective Using literature metrology,scientific literature in the field of depression models in animals was analyzed to better understand the development trends and hot topics in this field.Methods We obtained publications on depression and animal models from 2013 to 2022 from the Web of Science core set database.CiteSpace 6.1 R1(64-bit)Basic was used to analyze annual publications,countries,institutions,authors,and keywords related to this field.Results A total of 1000 articles were included in this study.From 2013 to 2022,the number of articles published increased gradually and then stabilized.In terms of the number of articles,the United States had the most published articles(256).Wegener Gregers was the most influential author in the field with 23 published articles.Conclusions The field focuses on signaling pathways and therapeutic approaches to determine the pathogenesis of depression and better treatments.This study provides a visual analysis of trends in depression research to help researchers keep up with the latest developments.

Evaluation of behavioral responses to restraint stress in the house mouse (Mus musculus musculus) of wild origin

Stress is a fundamental concept for many areas of animal research. In laboratory rodents, exposure to various stressors results in immediate and postponed behavioral changes that can be measured with standard tests. Less is known about how wild rodents that have not undergone domestication respond to stressors in laboratory settings. This study was aimed at evaluating behavioral responses to restraint stress in male and female wild-derived house mice (Mus musculus musculus). One week after the end of three daily restraint sessions, alterations in mouse behavior were assessed in two tests. In the open field test, stressed mice (n = 23) entered the unprotected central zone less frequently (P < 0.05) and showed increased duration of self-grooming (P < 0.05) compared to controls (n = 23), indicating elevated anxiety. In the forced swim test, most mice (44 out of 46) displayed episodes of behavioral despair, but the influence of stress was insignificant. To characterize baseline performance of wild-derived mice, their behavior was compared to that of a laboratory strain. As compared to C57BL/6 males (n = 10), M. m. musculus males (n = 14) showed significantly greater exploratory activity in the open field and longer latency of the first immobility episode in the forced swim test (P < 0.001). Overall, these findings confirm ecological validity of the widely used animal model of restraint stress and may serve as a basis for future studies.

Randomized experimental study of topical vasodilators in microsurgery with cost analysis / Estudo experimental randomizado de vasodilatadores tópicos em microcirurgia com análise de custo

ABSTRACT Objective: Throughout microsurgical anastomosis, many surgeons use topical vasodilators in order to reduce pathological vasospasm. It was carried out an experimental study comparing the effectiveness of topical use of Nitroglycerin, Papaverine, Magnesium sulfate over a control group in the femoral artery and vein of rats, in reducing prolonged vasospasm. Methods: Randomized comparative experimental study in 15 rats, divided into four groups. The external diameter of the vases soaked in the randomized solution was measured. For statistical analysis, it was calculated the percentual increase in the external diameter of the vessels. Results: A statistically significant increase in arterial dilation was observed after 10 minutes of topical application of 10% magnesium sulfate compared to the control group, with p = 0.044 . No other drug showed a vasodilator effect superior to the control group. Magnesium sulfate at 10% is still not used in microsurgery and costs 15 times less than papaverine, the standard drug for topical vasodilation in clinical cases at our service. Conclusion: Magnesium sulfate had better vasodilating effects over the control group after 10 minutes of arterial microanastomosis. None of the tested drugs have presented superior vasodilating effects over each other nor the control group after venous microanastomosis. Level of evidence II, Experimental study, Randomized Trial.

RESUMO Objetivo: Durante a anastomose microcirúrgica, muitos cirurgiões utilizam vasodilatadores tópicos para reduzir o vasoespasmo prolongado patológico, assim reduzindo o risco de complicações vasculares. Entretanto, ainda faltam dados experimentais para identificação da droga padrão-ouro para vasodilatadores tópicos em microcirurgia e sua avaliação de análise de custo, já que a droga geralmente utilizada para este objetivo é baseada, na maior parte dos casos, na experiência do cirurgião. Métodos: Foi realizado um estudo experimental comparativo randomizado, avaliando a eficácia do uso tópico de Nitroglicerina, Papaverina e Sulfato de Magnésio em relação a um grupo controle, na redução do vasoespasmo na artéria e veia femoral de ratos. Foram avaliados o diâmetro externo dos vasos embebidos em solução randomizada dos fármacos para vasodilatação. Após cálculo do aumento percentual no diâmetro externo dos vasos, foi realizada análise estatística. Resultados: Observou-se aumento estatisticamente significativo da dilatação arterial após 10 minutos de aplicação tópica de sulfato de magnésio a 10% em relação ao grupo controle, com p = 0,044. Nenhuma outra droga apresentou efeito vasodilatador superior ao grupo controle. O sulfato de magnésio a 10% ainda não é utilizado em microcirurgia e apresenta custo até 15 vezes menor quando comparado com a papaverina, droga padrão para vasodilatação tópica em casos clínicos em nosso serviço. Conclusão: O sulfato de magnésio apresentou melhor efeito vasodilatador quando comparado ao grupo controle, após 10 minutos da microanastomose arterial. Nenhum dos fármacos testados apresentou efeito vasodilatador superior após a microanastomose venosa. Nível de Evidência II, Estudo experimental, Ensaio Randomizado.

The effect of low dose intra-articular S(+) ketamine on osteoarthritis in rats: an experimental study

Abstract Background: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. Methods: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. Results: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. Conclusion: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB approval number: 23115 012030/2009-05.

Modelos pré-clínicos de câncer hepático / Preclinical models of liver câncer

ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.

Impacto do treinamento físico no perfil inflamatório e redox renal no desenvolvimento de síndrome metabólica / Impact of exercise training on inflammatory and redox renal profiles in metabolic syndrome development

Objetivo: Investigar o efeito do treinamento físico aeróbio (TF) no perfil inflamatório e de estresse oxidativo renal em modelo experimental de desenvolvimento de síndrome metabólica (SM). Métodos: Ratos Wistar e espontaneamente hipertensos (SHR) distribuídos nos grupos: controle (C), hipertenso (H), hipertenso frutose (HF) e hipertenso frutose treinado (HFT). Os grupos HF e HFT foram submetidos à sobrecarga de frutose (10%, 60 dias) desde o desmame. O TF foi realizado em esteira por 60 dias (5dias/semana, 40-60% velocidade máxima do teste de esforço). Resultados: O TF promoveu redução de ânion superóxido, peróxido de hidrogênio e proteínas oxidadas comparado ao grupo HF. Além disso, o grupo HFT apresentou aumento de FRAP e nitritos comparado aos grupos H e HF. No perfil inflamatório, o TF proporcionou aumento de IL-10 e redução da razão TNFα/IL-10. Conclusão: Os resultados demostraram que o treinamento aeróbio atenuou o estresse oxidativo e favoreceu um perfil anti-inflamatório no tecido renal em um modelo de desenvolvimento de SM.

Objective: To investigate the effect of aerobic exercise training (ET) on renal inflammatory and oxidative stress profiles in an experimental model of metabolic syndrome (MS) development. Methods: Wistar and spontaneously hypertensive (SHR) rats were distributed into control (C), hypertensive (H), hypertensive fructose (HF) and trained hypertensive fructose (THF) groups. The HF and THF groups were submitted to fructose overload (10%, 60 days) since weaning. The ET was performed on a treadmill for 60 days (5 days/week, 40-60% maximum speed of the exercise test). Results: The ET promoted reduction in renal superoxide anion, hydrogen peroxide and oxidized proteins compared to the HF group. In addition, the THF group showed an increase in FRAP and in nitrites compared to the H and HF groups. In the inflammatory profile, ET provided an increase in IL-10 and a reduction in TNFα/IL-10 ratio. Conclusion: The results showed that aerobic training attenuated oxidative stress and favored an anti-inflammatory profile in renal tissue in a model of MS development.

Adicción al tabaco y adolescencia: riesgos psicobiológicos / Psychobiological risks of tobacco during adolescence. A narrative review

Resumen La investigación moderna, tanto en humanos como preclínica, que utiliza modelos animales indica que fumar durante la edad adolescente resulta en cambios cerebrales y psicológicos a corto y largo plazo en el fumador, así como en un aumento significativo en los riesgos de desarrollar adicción al tabaco durante la vida. Por lo tanto, en la presente revisión narrativa se describirán y profundizarán los hallazgos investigativos modernos de la psicobiología de la adolescencia y los efectos del tabaco en el desarrollo, con un énfasis particular en la comprensión de los efectos psicológicos y cerebrales del consumo de tabaco durante la adolescencia, tanto a corto como a largo plazo. Se considerarán de manera detallada los avances investigativos sobre la psicobiología de la adolescencia y sus riesgos en las adicciones desde los aspectos: conductual, cognitivo, reactividad al estrés y psicobiología. Sobre esta base, se revisará la investigación sobre la psicobiología de la adolescencia y la evidencia de vulnerabilidad a la adicción durante esta etapa. Al final, se abordarán los efectos del tabaco en el cerebro y conducta durante el desarrollo adolescente y vida posterior, ya que se ha encontrado evidencia relacionada con alteraciones cerebrales crónicas en los sistemas colinérgicos y regiones cerebrales asociadas con la dependencia de la nicotina. Se espera que la revisión y divulgación de esta información en el idioma español sea de valor para la comprensión de los problemas de vulnerabilidad y predisposiciones a la adicción al tabaco en el contexto de Latinoamérica.

Abstract Tobacco use and its harmful health-related problems have become one of the largest modern preventable public health issues. Current research strongly suggests that smoking during adolescence enhances addictive smoking behaviors during life, which can be related to adolescence as a critical ontogenetic period characterized by behaviors that can increase the probability of risk-related behaviors such as sensation and novelty seeking. Adolescent development is also a period of maturation of frontal and subcortical neural systems, brain changes that underlie higher impulsivity tendencies to promote adequate learning and adaptations necessary to succeed the novel challenges of the adult life, but those changes also enhance vulnerabilities to the addictive effects of drugs. Consistent with this, tobacco use affects brain development processes which underlie long-term psychobiological alterations and the enhanced risks for tobacco addiction during adult life. Thus, the present review describes current psychobiological approaches to understand general addiction processes and tobacco addiction, highlighting the behavioral and neural short-term effects of tobacco use during adolescence and its long-term effects during adulthood. Current research has advanced on four aspects for the understanding of both the psychobiology of adolescent development and the effects of drugs of abuse during this time. The first aspect is behavioral, as adolescence is related to important changes on motivational and emotional behaviors such as sensation seeking. Other important behavioral changes are social approach, a higher variety of opportunity for personal choices, and development of personal independence. Research on a second aspect has focused on cognition. A review of research is presented showing enhanced abilities during adolescence development for reading, abstract and logical thinking, and novel problem solving. Stress reactivity is the third aspect of reviewed psychobiological mechanisms. The stress biological system undergoes important changes during adolescence, including changes on stress-related hormones and neural architecture. An important issue is that exposure to early and/or chronic stressful circumstances during adolescence could be related to higher risk to the start and maintenance of addiction states, as suggested by research assessing the disruptive effects of stress on psychobiological homeostatic processes needed to maintain stable biological and emotional regulation. The fourth aspect is psychobiology. In this section research is reviewed related to the development of monoaminergic brain circuits underlying motivation, novelty-seeking, impulsivity, and addiction processes. Using as model the previous review integration, the effects of nicotine are discussed, the essential addictive component of tobacco, on the neurochemical systems underlying tobacco addiction. Following this, important research is introduced that describes psychobiological changes during adolescence and evidence of vulnerability to addiction during this life stage. Then, current research on both short-term and long-term effects of tobacco or nicotine administration during adolescence on the brain, behavior, and cognition is introduced. The current research advances and discussions on the psychobiology of addictions in general, and tobacco addiction in particular, have been possible to a large extent from the use of animal models and preclinical research, since animal models have become crucial to identify learning, motivational, emotional, and cognitive mechanisms that underlie addictive processes, and making possible to perform experimental procedures to discover the functioning and participation of biological components. One example of such components is the cholinergic system, which is activated by nicotine and is part of the neurochemical machinery on different brain areas important for both tobacco addiction and adolescence development such as the dorsal striatum, amygdala, ventral tegmental area, nucleus accumbens, prefrontal cortex, and hippocampus. The present review and research divulgation written in Spanish are expected to clarify modern research on addiction and encourage current scientific education on the vulnerabilities and predispositions for tobacco abuse in Latin-American countries.

Animal models of anxiety: a review

Anxiety is a disorder that affects the quality of life and also imposes a huge economic burden. Animal models of anxiety have widened our understanding of the pathophysiology behind anxiety and to identify newer pharmacological compounds. Every behavioral test has its own limitations, and there are ways to minimize these like environment and handling. This review lists various experimental models of anxiety based on unlearned ethological models, learned responses like the Vogel conflict test, and psychological and physical stress models.

Comparison of three methods for establishing rat peri-implantitis model / 北京大学学报(医学版)

OBJECTIVE@#To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods.@*METHODS@#Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1β (IL-1β). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death.@*RESULTS@#After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1β in the test groups were higher than those in the control group (P < 0.05).@*CONCLUSION@#Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.

Research progress on genetic model of mouse with glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

Glaucoma, currently the world's first irreversible blindness, is a complex multifactorial disease with a genetic predisposition, and pathologically elevated intraocular pressure is its risk factor. The pathogenesis of glaucoma is not fully understood, and most existing studies are based on animal models, with mice as the main research object, and the pathological damage process of glaucoma is reconstructed through experimental induction means or transgenic manipulation to further investigate the relevant pathogenesis and pathological changes. The technique of experimentally induced construction of glaucoma mouse models has been studied by many scholars and is gradually becoming mature. And as research in molecular biology and genetics has advanced, more and more studies have focused on the disease genes associated with glaucoma, and transgenic mouse models have become a hot topic in recent years. In contrast to experimental manipulation to control a single factor, gene editing is better able to simulate the complex process of disease pathogenesis. This paper focuses on providing a more complete direction and strategy for model selection in the future research by describing the progress of research on relevant transgenic mouse model of glaucoma.

"Disease-syndrome-therapy" Spontaneous Abortion Models and Application Trends of Single-cell Multimodal Omics： A Review / 中国实验方剂学杂志

The incidence of spontaneous abortion （SAB） has been increasing year by year， and its etiology is complex， with limited treatment options， which poses a serious threat to social stability. The "disease-syndrome-therapy" research model can significantly improve the clinical efficacy of traditional Chinese medicine （TCM） for preventing miscarriage， but there has always been a lack of key and recognized diagnostic and treatment evaluation markers， which need to be further explored to establish a scientific and unified evaluation standard system. It is proposed to collect existing "disease-syndrome-therapy" SAB animal models， transplant and improve the model evaluation indicators， evaluate the degree of match between SAB animal models and the clinical characteristics of TCM and Western medicine diseases and syndromes， and compare the advantages and disadvantages of different SAB animal models in terms of construction methods， target selection， and evaluation indicators. In addition， the frontiers of TCM experimental research will be explored. In view of the current status and related bottlenecks of molecular biomarkers research on SAB TCM animal models， a single-cell multimodal omics research strategy will be proposed to break through the related evaluation defects of the "disease-syndrome-therapy" SAB and analyze the differences in various cell types， cell subpopulations， spatiotemporal trajectories， and gene expression in the mother-fetal interface tissue at the single-cell level. This will provide accurate guidance and model animal platform support for the in-depth study of disease-syndrome models， Zang-fu biology， and novel targeted drugs. It will also provide a basis for establishing a stable and repeatable "disease-syndrome-therapy" SAB animal model and evaluation indicator system， which is beneficial for the long-term development of TCM reproductive animal model research.

Advances in animal models of chronic heart failure and its applications in traditional Chinese medicine / 中国中药杂志

Chronic heart failure(CHF) is a series of clinical syndromes in which various heart diseases progress to their end stage. Its morbidity and mortality are increasing year by year, which seriously threatens people's life and health. The diseases causing CHF are complex and varied, such as coronary heart disease, hypertension, diabetes, cardiomyopathy and so on. It is of great significance to establish animal models of CHF according to different etiologies to explore the pathogenesis of CHF and develop drugs to prevent and treat CHF induced by different diseases. Therefore, based on the classification of the etiology of CHF, this paper summarizes the animal models of CHF widely used in recent 10 years, and the application of these animal models in traditional Chinese medicine(TCM) research, in order to provide ideas and strategies for studying the pathogenesis and treatment of CHF, and provide ideas for TCM modernization research.