Advances in viral encephalitis:Viral transmission,host immunity,and experimental animal models

Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.

Advances in cytokine-mediated mechanisms for cardiac regeneration and repair post-myocardial infarction:a comprehensive review

Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studies have shown that cytokines participate in cardiac regeneration and repair by modulating cellular proliferation,differentiation,and apoptosis post-MI.Here,we explored the crucial role of cytokines in cardiac regeneration and repair processes in experimental animal models,detailing how cytokines modulate cellular mechanisms involved in repairing cardiac tissue post myocardial infarction(MI).Specifically,it highlights the activation of cardiac stem cells and progenitors,the regulation of inflammatory responses to prevent excessive damage,and the involvement in matrix remodeling to ensure functional integrity of the heart.This comprehensive examination underscores the therapeutic potential of enhancing cytokine secretion to mitigate adverse effects and promote recovery following MI,offering insights into possible interventions that could improve patient outcomes in clinical settings.

Establishment of Bacterial Lobular Pneumonia Model in Mice

In this study cortisol and cyclophosphamide were injected into abdominal cavities of mice to keep them in an immunosuppressive state. Then the pathogen Klebsiella pneumoniae was given to infect the lungs and the experimental modcl of lobular pneumonia in the mice was thus established successfully.The experimental animal model has typical pathologic manifestation and good replication and can be used to to study the effect of drugs.

Photodynamic diagnostics of early gastric cancer:Complexity measures of gastric microcirculation and new model of metastatic adenocarcinoma of rat stomach

The detection of early gastric cancer that often develops asymptomatically is crucial for improving patient survival.The photodynamic diagnosis(PDD)of gastric cancer using 5-aminolevulinic acid/protoporphyrin IX(5-ALA/PpIX)has been reported in several studies.However,the selectivity of PDD of gastric tumor is poor with often false-positive results that require the development of new methods to improve PDD for early gastric cancer.Therefore,a measure of the complexity of gastric microcirculation(multi-scale entropy,MSE)and the detrendedfluctuation analysis(DFA)were applied as additional tools to detect early gastric cancer in rats.In this experimental study,we used our original model of metastatic adenocarcinoma in the stomach of a rat.To induce a gastric tumor,we used a long-term combination(for 9 months,which is 1/2 of the life of rats)of two natural factors,such as chronic stress(overpopulation being typical for modern cities)and the daily presence of nitrites in food and drinks,which are common ingredients added to processed meat andfish to help preserve food.Our results clearly show that both methods,namely,PDD using 5-ALA/PpIX and complexity/correlation analysis,can detect early gastric cancer,which was confirmed by histological analysis.Pre-cancerous areas in the stomach were detected as an intermediatefluorescent signal or MSE level between normal and malignant lesions of the stomach.However,in some cases,PDD with 5-ALA/PpIX produced a false-positivefluorescence of exogenousfluorophores due to its accumulation in benign and inflammatory areas of the mucosa.This fact indicates that the PDD itself is not sufficient for the correct diagnosis of gastric cancer,and the use of additional characteristics,e.g.,complexity measures or scaling exponents,can significantly improve the diagnostic accuracy of PDD of gastric cancer that should be confirmed in further clinical studies and applications.

EVALUATION OF RAT MODEL OF CHRONIC GLAUCOMA BY LIGATING EPISCLERAL VEINS

Objective To develop and evaluate the rat model of chronic glaucoma by episcleral veins ligation （EVL）. Methods Experimental glaucoma was induced unilaterally in 28 male Sprague-Dawley rats by ligating two episcleral veins. Intraocular pressure （10P） in rats was measured by a Goldmann applanation tonometer under 3 % pentobarbital sodium anesthesia. The optic nerve head and retinal vasculature were assessed by repeated fundus examinations. The amount of optic nerve axons was assessed by Image-Pro Plus image analysis system in a masked fashion. Results lOP without EVL was （ 19.21 ± 1.23） mmHg, whereas the EVL eyes gained about 1.8-fold higher 10P[ （33.96 ±2. 73） mmHg]after EVL immediately （ P 〈 0. 001 ）. The elevated IOP gradually decreased over time. However, the differences were kept significant up to 8 weeks after EVL. The lOP was reduced to similar levels as contralateral eyes at 12 and 16 weeks after EVL. The glaucomatous optic nerve excavation appeared in EVL eyes at 8 weeks after EVL, and the optic nerve excavation enlarged gradually with the increasing post-operation time. The amount of optic nerve axons also significantly decreased in EVL eyes at 8 weeks after EVL, and the amount of axons decreased gradually with the increasing post-operation time. Conclusion Increase of lOP caused by EVL represents a useful and efficient model of experimental glaucoma in rats.

High-dose dietary zinc promotes prostate intraepithelial neoplasia in a murine tumor induction mode

To evaluate the role of high-dose dietary zinc in the process of prostate malignancy,60 Sprague-Dawley rats were randomly divided into four groups：tumor induction with carcinogen and hormone （group 1）,oral zinc administration without tumor induction （group 2）,oral zinc administration with tumor induction （group 3） and a control without zinc administration or tumor induction （group 4）. Zinc was supplied orally in the form of zinc sulfate heptahydrate dissolved in drinking water to groups 2 and 3 for 20 weeks. Although the serum level of zinc measured at 20 weeks was maintained similarly in each group （P = 0.082）,intraprostatic zinc concentrations were statistically different. Group 1 prostates contained the least amount of zinc in both the dorsolateral and ventral lobes at levels of 36.3 and 4.8 μg g^-1,respectively. However,in group 3,zinc levels increased in both lobes to 59.3 and 12.1 μg g^-1,respectively,comparable with that of group 4 （54.5±14.6 and 14.1±2.4 μg g^-1）. In spite of these increases in zinc concentration,the prevalence of prostate intraepithelial neoplasm was rather increased in group 3 （53.3% and 46.7%） compared with group 1 （33.3% and 33.3%） in both dorsolateral and ventral prostate lobes. Although prostate intraepithelial neoplasm did not develop in any prostate in group 4,zinc administration did induce prostate intraepithelial neoplasm in group 2 （46.7% and 40.0%）. Thus,although high dietary zinc increased intraprostatic zinc concentrations,it promoted,instead of preventing,prostate intraepithelial neoplasm in a murine prostate malignancy induction model.

Improved Cardiac Contractility of Human Recombinant Growth Hormone on the Congestive Heart Failure of Pig

The enhanced cardiac contractility effect of human recombinant growth hormone (hr-GH) on the congestive heart failure (CHF) was studied on the pig. To build a pig model of congestive heart failure, a temporary artificial cardiac pacemaker was implanted in the pig’s body and paced at 220 beats to 240 beats per minute for 1 week. After the model of congestive heart failure was successfully set up, the frequency of the pacemaker was changed to 150 beats to 180 beats per minute to maintain the CHF model stable. Pigs were divided into three groups: The hr-GH group in which 0.5 mg/kg per day of hr-GH was administrated intramuscularly for 15 days, the injection control group in which an equal amount of physiological saline was injected intramuscularly, and a normal control group. The left ventricular diastolic end pressure was (10.60±2.41) mmHg in the hr-GH group, but (19.00±3.81) mmHg in the saline control group (P<0.01); Cardiac output was (1.86±0.13) L/min in the hr-GH group, but (1.56±0.18) L/min in the saline control group (P<0.05); Peripheral vascular resistance was (56.88±7.51) mmHg·(L/min) -1 in the hr-GH group, whereas (70.30±11.59) mmHg·(L/min) -1 in the saline control group (P<0.05); +dp/dt max was (2900±316.23) and (2280±286.36) in the hr-HG group and the saline control group respectively (P<0.05). The results show that hr-GH enhances myocardial contractility of CHF, and the CHF model built by a temporary artificial cardiac pacemaker at a high rate of stimulation is reasonable and applicable.

Catheter Ablation of AV Conduction Using Radiofreguency Current in Atrial Tachy-arrhythmias

In this study cortisol and cyclophosphamide were injected into abdominal cavities of mice to keep them in an immunosuppressive state. Then the pathogen Klebsiella pneumoniae was given to infect the lungs and the experimental modcl of lobular pneumonia in the mice was thus established successfully.The experimental animal model has typical pathologic manifestation and good replication and can be used to to study the effect of drugs.

Research progress on iron homeostasis regulation and heart-related diseases

Iron is an indispensable trace element in mammals and performs several important physiological functions in the body.Dynamic equilibrium in iron metabolism exists.Iron uptake,storage,and output are in equilibrium as well.Several laboratory animal models have shown that iron deficiency and deposition can lead to a variety of functional disorders.Cardiac diseases caused by iron deposition in laboratory animal models are caused by abnormal oxidative stress,electrophysiological changes,iron metabolism-related gene defects,myocardial cell apoptosis,fibrosis,ferroptosis,and other causes.This review discusses the causes of heart disease related to iron deposition in laboratory animal models to illustrate further the impact of effective iron removal therapy on cardiac disease associated with iron deposition.In addition,this review demonstrates the possibility of elucidating the precise molecular mechanism of iron abnormality in heart diseases in experimental animal models and the feasibility of using iron abnormality as a target for developing new therapeutic drugs for the treatment of heart disease.

Validation of glaucoma-like features in the rat episcleral vein cauterization model

Background Glaucoma,an irreversible optic nerve neuropathy,always results in blindness.This study aimed to evaluate glaucoma-like features in the rat episcleral vein cauterization （EVC） model by multiple in vivo and in vitro evidences.Methods Wistar rat was used in this study.The elevated intraocular pressure （IOP） was induced by cauterization of three episcleral veins.lOP was monitored with Tono-Pen XL tonometer.Time-dependent changes to the neuronal retinal layers were quantified by Fourier domain-optical coherence tomography.The function of retina was evaluated by electroretinogram （ERG）.Survival of retinal ganglion cells （RGCs） was quantified by retrograde labeling.Histology study was performed with retinal sections stained with hematoxylin-eosin,glial fibrillary acidic protein,and neuronal nuclear antigen.Retina and aqueous humor protein were extracted and cytotoxic protein tumor necrosis factor alpha （TNF-α） and alpha-2 macroglobulin （α2m） were measured with Western blotting.Results EVC is a relatively facile intervention,with low failure rates （＜5％）.After surgical intervention,chronic mild lOP elevation （about 1.6-fold over normal,P ＜0.05） was induced for at least 6 weeks without requiring a second intervention.High lOP causes chronic and progressive loss of RGCs （averaging about 4％ per week）,progressive thinning of neuronal retinal layers （3-5 μm per week）,and reduction of a-and b-wave in ERG.EVC method can also induce glial cell activation and alterations of inflammation proteins,such as TNF-α and α2m.Conclusion EVC method can establish a robust,reliable,economic and highly reproducible glaucomatous animal model.

Pathological observation of brain arteries and spontaneous aneurysms in hypertensive rats

Objective To investigate the role of hypertension in the pathogenesis of cerebral aneurysms in rats.Methods Twenty spontaneous hypertensive rats (SHR) and 10 Wistar-Kyoto rats (WKY) were included in this observational study. Animals were fed with normal diet and drinking water. No experimental modifications were undertaken in either group. They were sacrificed at one year of age, the bifurcations of the circle of Willis were dissected and longitudinal serial sections were prepared for light microscopic and transmission electron microscopic study.Results In the SHR group, 2 of the 20 rats formed an aneurysm respectively at the bifurcations of the basilar artery. As revealed by electron microscopy, injury at the bifurcation of the artery first occurred on the steeper side of the intimal pad. Furthermore, loss of endothelial cells, small depressions on the intima, disruptive internal elastic lamina and lymphocytes or red blood cells infiltration were noted at the steeper side of the intimal pad. No significant changes were observed in WKY group.Conclusions Cerebral aneurysms can form spontaneously in SHR without ligation of the common carotid artery and without a diet containing β-aminoproprionitrile. Long-standing systemic arterial hypertension is one of the etiological factors that contributes to aneurysm formation in SHR rats.