Fundus photography,fluorescein angiography,optical coherence tomography and electroretinography of preclinical animal models of ocular diseases

The eye is an immune-privileged and sensory organ in humans and animals.Anatomical,physiological,and pathobiological features share significant similarities across divergent species(1).Each compartment of the eye has a unique structure and function.The anterior and posterior compartments of the eye contain endothelium(cornea),epithelium(cornea,ciliary body,iris),muscle(ciliary body),vitreous and neuronal(retina)tissues,which make the eye suitable to evaluate efficacy and safety of tissue specific drugs(2).

Animal models of coronary heart disease

Cardiovascular disease,predominantly coronary heart disease and stroke,leads to high morbidity and mortality not only in developed worlds but also in underdeveloped regions.The dominant pathologic foundation for cardiovascular disease is atherosclerosis and,as to coronary heart disease,coronary atherosclerosis and resulting lumen stenosis,even total occlusions.In translational research,several animals,such as mice,rabbits and pigs,have been used as disease models of human atherosclerosis and related cardiovascular disorders.However,coronary lesions are either naturally rare or hard to be fast induced in these models,hence,coronary heart disease induction mostly relies on surgical or pharmaceutical interventions with no or limited primary coronary lesions,thus unrepresentative of human coronary heart disease progression and pathology.In this review,we describe the progress of animal models of coronary heart disease following either spontaneous or diet-accelerated coronary lesions.

Call for papers of the special issue on Animal Models and Infectious Diseases

Primates and animal models are major areas of coverage for Zoological Research （ZR）. Over the past few years, ZR has released a series of special issues/topics addressing various aspects of these areas, e.g., ge- netics, immunology, and physiology neuroscience. A special issue for 2017 focusing on ＂Animal Models of Infectious Diseases＂ is under preparation and, so far, includes original research articles and reviews on filo- viruses and coxsackievirus involving guinea pigs, mice, and other species. Further to this, ZR would like to extend a very warm invitation to all peer researchers in the field to submit outstanding work to the journal on this special issue.

Whole mount of adult ear skin as a model to study vascular malformations

Background:Genetic analysis in human patients has linked mutations in PIK3CA,the catalytic subunit of PI-3′Kinase,to sporadic incidences of vascular malformations.Methods:We have developed a mouse model with inducible and endothelial-specific expression of PIK3CA H1047R,resulting in the development of vascular malformations.Systemic induction of this mutation in adult mice results in rapid lethality,limiting our ability to track and study these lesions;therefore,we developed a topical and local induction protocol using the active metabolite of tamoxifen,4OH-T,on the ear skin of adults.Results:This approach allows us to successfully model the human disease in a mature and established vascular bed and track the development of vascular malformations.To validate the utility of this model,we applied a topical rapamycin ointment,as rapamycin is therapeutically beneficial to patients in clinical trials.We found that the induced ear lesions showed significant attenuation after treatment,which was easily quantified.Conclusions:These data collectively provide evidence of a new model to study vascular malformations in adult tissues,which should be particularly useful in environments lacking specialized small-animal imaging facilities.

Expression of cyclooxygenase-2 and its pathogenic effects in nonalcoholic fatty liver disease

Objective：To investigate the expression of cyclooxygenase-2 and its pathological effect in the experimental nonalcoholic fatty liver of rats, and to explore its possible mechanism. Methods：The rat NAFLD model was established by giving a fat-enriched diet. The blood samples were obtained form abdominal aorta and the levels of serum ALT, AST and IL-1, changes in the hepatic tissue 6-k-PGF1 α TXB2 were measured. The expression level of COX-2 in rats livers were assayed by immunohistochemistry, RT-PCR and Westernblot. Results： Light microscope analysis revealed that hepatocytes were injured in the model group and slightly in the treatment group. The levels of serum TXB2 and IL-1 in the fatty liver rats were increased. Compared with the model group, the IL-1 and TXB2 increased significantly（P〈 0.05）, on the contrary, compared with the normal group, the hepatic tissue 6-Keto-prostagland decreased significantly in the model group（P 〈 0.05）, the treatment group also increased but P 〉 0.05. There was no positive expression of COX-2 in hepatic tissue of normal rats. In the model group, there was positive expression of COX-2 antigen and the number of COX positive cells progressively increased at 4, 8, 12 wks. The intensity of expression of COX-2 had significantly increased（P 〈 0.05 ） and the intensity of COX-2 expression in the treated group decreased remarkably compared with the model group（P 〈 0.05）. The expression of COX-2 mRNA and the level of COX-2 protein were significantly stronger in the liver of model rats compared with normal rats, and significantly weaker in treated rats, than in 8W and 12W model rats（P 〈 0.05）. Conclusion：The increase of COX-2 expression in NAFLD is closely associated with the severity of liver inflammation and damage. COX-2 may play an important role in the progression of rat NAFLD, and the expression of COX-2 mRNA is downregulated by cyclooxygenase-2 inhibitor, which can depress the oxidative stress and control inflammatory response efficiently.

Comparison of Three Experimental Models for Rat Osteoarthritis Induction

Background: Osteoarthritis is a slowly progressive and debilitating disease with high prevalence in adult population. Knee is one of the joints most affected by this disorder. There are several models for animals’ osteoarthritis induction, however it is not identified any paper that compares these techniques. The present study was aimed to define the most appropriate model for rats osteoarthritis induction. Material and Methods: 40 Wistar rats were distributed into 4 groups of 10 animals each: normality group (NG);meniscectomy group (MG);quinolone group (QG) and iodoacetate group (IG). Radiographic images of the rat’s knees were analyzed as well as the amount of chondrocytes in the epiphyseal and articular cartilage. Results: In the radiographic analysis, there was a low correlation between the raters. Regarding the amount of chondrocytes in the epiphyseal cartilage, it was noticed that the IG and QG groups had fewer chondrocytes than NG, in contrast to MG that reported similar results to normality (p > 0.05). There was no significant difference between IG and QG groups (p > 0.05). Regarding the amount of chondrocytes in articular cartilage, it was noticed that the IG group showed fewer chondrocytes than NG (p 0.05). There was no significant difference between QG and MG groups (p > 0.05). Conclusion: Intraarticular injection of iodoacetate in rats is the model with greatest effect on reduction of chondrocytes amount.

A new rat model of portal hypertension induced by intraportal injection of microspheres

ＡｎｅｗｒａｔｍｏｄｅｌｏｆｐｏｒｔａｌｈｙｐｅｒｔｅｎｓｉｏｎｉｎｄｕｃｅｄｂｙｉｎｔｒａｐｏｒｔａｌｉｎｊｅｃｔｉｏｎｏｆｍｉｃｒｏｓｐｈｅｒｅｓＬＩＸｉａｎｇＮｏｎｇ１，ＩＳＢｅｎｊａｍｉｎ２ａｎｄＢＡｌｅｘａｎｄｅｒ２Ｓｕｂｊｅｃｔｈｅａｄ...

Adult hippocampal neurogenesis and its impairment in Alzheimer's disease

Adult neurogenesis is the creation of new neurons which integrate into the existing neural circuit of the adult brain.Recent evidence suggests that adult hippocampal neurogenesis(AHN)persists throughout life in mammals,including humans.These newborn neurons have been implicated to have a crucial role in brain functions such as learning and memory.Importantly,studies have also found that hippocampal neurogenesis is impaired in neurodegenerative and neuropsychiatric diseases.Alzheimer’s disease(AD)is one of the most common forms of dementia affecting millions of people.Cognitive dysfunction is a common symptom of AD patients and progressive memory loss has been attributed to the degeneration of the hippocampus.Therefore,there has been growing interest in identifying how hippocampal neurogenesis is affected in AD.However,the link between cognitive decline and changes in hippocampal neurogenesis in AD is poorly understood.In this review,we summarized the recent literature on AHN and its impairments in AD.

Establishing a cat model of chronic optic nerve compression injury

BACKGROUND： An animal model of chronic optic nerve injury is necessary to further understand the pathological mechanisms involved. OBJECTIVE： To establish a stabilized, chronic, optic nerve crush model, which is similar to the clinical situation to explore histopathological and optic electrophysiological changes involved in this injury. DESIGN, TIME AND SETTING： A randomized and controlled animal trial was performed at Shanghai Institute of Neurosurgery from May to October 2004, MATERIALS： A BAL3XRAY undetachable balloon and Magic-BD catheter were provided by BLAT, France; JX-2000 biological signal processing system by Second Military Medical University of Chinese PLA, China; inverted phase contrast microscopy by Olympus, Japan. METHODS： A total of twenty normal adult cats were randomly assigned to control （n = 5） and model （n = 15） groups, according to different doses of contrast agent injected through balloons as follows： 0.2 mL injection, 0.25 mL injection, and 0.35 mL injection, with each group containing 5 animals. Imitating the clinical pterion approach, the optic nerves were exposed using micro-surgical methods. An engorged undetachable balloon was implanted beneath the nerve and connected to a catheter. Balloon size was controlled with a contrast agent injection （0.1 mL/10 min） to form an occupying lesion model similar to sellar tumors. MAIN OUTCOME MEASURES： The visually evoked potential examination was used to study optical electrophysiology changes in pre-post chronic optical nerve injury. Ultrastructural pathological changes to the optic nerve were analyzed by electron microscopy. RESULTS： During the early period （day 11 after modeling）, visually evoked potential demonstrated no significant changes. In the late period （day 51 after modeling）, recorded VEP demonstrated that P1 wave latency was prolonged and P1 wave amplitude was obviously reduced. Following injury, the endoneurium, myelin sheath, lamella, axolemma, and axon appeared disordered. CONCLUSION： Results demonstrated that the chronic, intracranial, optical nerve crush model was stable and could simulate optic nerve lesions induced by sellar tumors. Under the condition of chronic optical nerve crush, visually evoked potentials were aggravated.

An Experimental Rabbit Model of Rhegmatogenous Retinal Detachment

An experimental model of rhegmatogenous retinal detachment in rabbits was established to simulate the pathophysiologic condition of human RRD. 24 rabbits were randomly divided into 3 groups and underwent vitrectomy with a vitrector and/or retinotomy with a Charles flute needle, with 12 in group Ⅰ (vitrectomy and retinotomy), 7 in group Ⅱ (retinotomy) and 5 in group Ⅲ (vitrectomy). All animals underwent follow-up examinations with direct and indirect ophthalmoscopy and fundus photography 12 h and day 1, 3, 5, 7, 10, 14, 21, and 28 after the procedure(s). Retinal changes were recorded. As a result, 10 RRDs were successfully established in group Ⅰ. Direct and indirect ophthalmoscopy and fundus photography demonstrated typical features of RRD. No RRD developed in group Ⅱ and Ⅲ. It was concluded that the experimental rhegmatogenous retinal detachment produced in a rabbit model after vitrectomy with retinotomy in this study was a convenient and reliable one. This RRD model mimicked the typical pathophysiological changes in humans.

An everlasting role of animal models in understanding human disease

Model organisms have been widely used to dissect important biological phenomena, as well as to explore potential causes and treatments for human disorders. Much of our knowledge on molecular mechanisms underlying the heredity, development as well as physiology is largely derived from the researches of model organisms. We have witnessed an explosive increase in the development and application of genetic modified model organisms in the last decade.

Tumor radioimmunoimaging of chimeric antibody in nude mice with hepatoma xenograft

ＴｕｍｏｒｒａｄｉｏｉｍｍｕｎｏｉｍａｇｉｎｇｏｆｃｈｉｍｅｒｉｃａｎｔｉｂｏｄｙｉｎｎｕｄｅｍｉｃｅｗｉｔｈｈｅｐａｔｏｍａｘｅｎｏｇｒａｆｔＧＯＮＧＹｉ１，ＬＩＵＫａｎｇＤａ１，ＺＨＯＵＧｅ１，ＸＵＥＱｉｏｎｇ１，ＣＨＥＮＳｈａｏＬｉａｎｇ...

Platelets and platelet alloantigens:Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

Platelets play critical roles in hemostasis and thrombosis.Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states.Fetal and neonatal alloimmune thrombocytopenia(FNAIT)is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy.Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus,and ultimately lead to maternal alloimmunization.FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage.Proper diagnosis,prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies.Given the ethical difficulties in performing basic research on human fetuses and neonates,animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT.The aim of this review is to provide an overview on platelets,hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.

A Preliminary Investigation of the Possible Hypoglycemic Activity of Hibiscus rosa-sinensis

The hypoglycemic activity of an ethanol extract of Hibiscus rosa-sinsnsis was studied in glucose located rats. Afer a single dose of the extract, a slight but insignificant hypoglycemic effect was observed at 30 and 90 min. At 120 min it was mild but significant. After repeated administration of the extract (once a day for seven consecutive days) a statistically significant (P < 0 .001 ) reduction in blood glucose levels was observed at 30, 90 and 120 min after glucose loading. The average hypoglycemic activity, after repeated administration of 250 mg kg-1 leaf extract was 81 %, under similar conditions average activity of tolbutamide was 96%. At 250 mg·kg-1 the efficacy of the extract was found to be 84% of tolbutawhde (100mg·kg- 1 ). Repeated treatment of animals either with tolbutandde a sulphonylurea or H. rosa-sinensis caused a 2-3-fold improvement in glucose tolerance as compared to those receiving only once. These data suggest that the leaf extract acts like tolbutamide and the meehanism of action may be a stimulation of pancreatic hata cells to produce more insulin or an increase of the glycogen deposition in liver. It appeare that the active principle in the tested extract has the sulphonylurea Skeleton in which -SO2-NH-CO- group and the substituents (S1 and S2) may be the possible active sites responsible for its hypolycemic activity.

CCR5 gene expression in fulminant hepatitis and DTH in mice

ＣＣＲ５ｇｅｎｅｅｘｐｒｅｓｓｉｏｎｉｎｆｕｌｍｉｎａｎｔｈｅｐａｔｉｔｉｓａｎｄＤＴＨｉｎｍｉｃｅＧＵＯＢａｏＹｕ１，ＺＨＡＮＧＳｕＹｉｎｇ２，ＮａｏｆｕｍｉＭｕｋａｉｄａ３，ＡｋｉｈｉｓａＨａｒａｄａ３，ＫｏｕｊｉＫｕｎｏ３，ＷＡＮＧＪｉａｎ...

Development of a rat C6 brain tumor model

OBJECTIVE: To establish rat C6 brain-tumor models and find a simple reliable index to judge tumor volume. METHODS: C6 cell suspension (10 microl) containing 10 g/L agarose and 1 x 10(6) cells was injected into the right caudate nucleus of the rat brain by a stereotaxic method. After implantation, rats were observed and given MRI scans. Rats were perfused with paraformaldehyde trans-aorta at the 10th, 15th, 20th and 25th day and before natural death. All brains, lungs, spinal cords and tumors were sectioned and inspected. Tumor-containing samples were prepared histologically by hematoxylin and eosin (HE) stains. RESULTS: Fifty implanted rats had 100% yield of intracerebral growth, with distant metastasis of 0% to 4%. CONCLUSION: A rat C6 brain-tumor model was successfully established. Rat survival time is correlated with tumor volume and may be useful as an index of tumor size.

Varied response of the pulmonary arterial endothelium in a novel rat model of venous thromboembolism

Background The experimental studies of venous thromboembolism （V-rE） as an entity and the response of the pulmonary arterial endothelium after VTE are still rare. The objective of this study was to observe changes in the pulmonary arterial endothelium using a novel rat model of VTE. Methods Rats were allocated to the VTE （n=54） or control groups （n=9）. The left femoral vein was blocked using a microvessel clip to form deep vein thrombosis （DVT）. One, four or seven-day-old thrombi were injected into the right femoral vein to induce DV-r-pulmonary thromboembolism （DVT-PTE）. The rats were sacrificed 1, 4 or 7 days later （Dn （1,4,7） Pn（1,4,7） subgroups （n=6））, and the lungs were examined using light and electron microscopy. Results On gross dissection, the rate of DVT formation was higher on day 1 （D1Pn： 100%, 18/18） than day 4 （D4Pn： 83%, 15/18; X^2=5.900, P=0.015） or day 7 （DFPn： 44%, 8/18; X2=13.846, P=0.000）. On gross dissection, the positive emboli residue rate in the pulmonary arteries was lower in the D1Pn subgroup （39%, 7/18） than the D4Pn （73%, 11/15; X2=3.915, P=0.048） and DFPn subgroups （100%, 8/8; X2=8.474, P=0.004）; however, light microscopy indicated the residual emboli rate was similar in all subgroups. Hyperplasia of the pulmonary arterial endothelium was observed 4 and 7 days after the injection of one-day-old or four-day-old thrombi. However, regions without pulmonary arterial endothelial cells and intra-elastic layers were observed one day after injection of seven-day-old thrombi. Conclusions This novel model closely simulates the clinical situations of thrombus formation and is ideal to study pulmonary endothelial cell activation. The outcome of emboli and pulmonary arterial endothelial alterations are related to the age and nature of the thrombi.