Laboratory Animal Research最新文献

Background: A brain abscess in human beings is a focal infection of the central nervous system frequently characterized by areas of localized cerebritis and central necrosis surrounded by a well vascularized capsule. A brain abscess, although sporadically reported, is relatively rare disease in domestic animals (horses, cattle, goats and alpacas), companion animals (dogs and cats) and laboratory nonhuman primates. Brain abscesses are life threatening disease that needs early and aggressive veterinary therapy.

Case presentation: The purpose of this study on a brain abscess in a Japanese monkey was to report the investigational and therapeutic processes including clinical observations, hematological and serum biochemical profiles, and magnetic resonance imaging (MRI) features, probiotic and antibiotic therapy. In clinical observation, the monkey presented with slowly progressive gentle and depressed behavioral change. Hematological findings showed that slightly declined platelet counts gradually increased in the course of the treatment. Serum biochemical profiles revealed initial markedly elevated. A series of chemotherapy provide prominent relief from the influence of the brain abscess. MRI images illustrated that a brain abscess was located in the right frontal lobe and the mass was delineated by a thick rim, indicating the capsule formation stage. The lesion chronologically decreased in size over the course of treatment. Until 11 weeks after treatment of the brain abscess, the size of brain abscess continued to reduce, leaving an organized lesion trace. To the best of my knowledge, this is the first report on successful treatment for a brain abscess in a Japanese monkey (Macaca fuscata).

Conclusions: Medical management of simian brain abscesses is possible based on the controlled and resolving nature of the lesions as determined by MRI and completion of a of chemical antibiotic treatment presented in this study.

Background: Cerebral ischemia is a serious neurological disorder that can lead to high morbidity and mortality. Chlorogenic acid is a polyphenol compound with antioxidant that can regulate proteins in cerebral ischemia. Middle cerebral artery occlusion (MCAO) surgery was performed to induce ischemic brain injury and was maintained for 24 h. Chlorogenic acid (30 mg/kg) or vehicle was administrated into the peritoneal cavity 2 h after MCAO surgery. The cerebral cortical tissues were collected for further study and a proteomic approach was performed to identify the proteins changed by chlorogenic acid in the MCAO animals.

Results: We found that chlorogenic acid alleviated in changes in adenosylhomocysteinase, glycerol-3-phosphate dehydrogenase, eukaryotic translation initiation factor 4A-II, apolipoprotein A-I, and mu-crystallin. These proteins were reduced in MCAO animals with vehicle, and these reductions were attenuated by chlorogenic acid treatment. The mitigation of this reduction by chlorogenic acid was confirmed by the reverse transcription PCR technique. These proteins are associated with energy metabolism, protein synthesis, inflammation, and physiological metabolism. They are involved in the neuroprotective effect of chlorogenic acid. These results showed that chlorogenic acid alleviates the neurological disorders caused by MCAO and regulates the expression of proteins involved in neuroprotection.

Conclusions: Therefore, our findings provide evidence that chlorogenic acid plays a neuroprotective role in stroke animal models by controlling specific proteins.

Preclinical ischemic stroke studies extensively utilize the intraluminal suture method of middle cerebral artery occlusion (MCAo). General anesthesia administration is an essential step for MCAo, but anesthetic agents can lead to adverse effects causing death and making a considerable impact on inducing cerebral ischemia. The purpose of this study was to comparatively assess the effect of isoflurane and xylazine on transient cerebral ischemia in a mouse model of MCAo. Twenty animals were randomly divided into four groups: sham group (no MCAo), control group (MCAo under isoflurane, no agent till reperfusion), isoflurane group (MCAo under isoflurane continued till reperfusion), xylazine group (MCAo under isoflurane, and administration of xylazine till reperfusion). The survival rate, brain infarct volume, and neurologic deficits were studied to assess the effect of isoflurane and xylazine on the stroke model. Our results showed that the body weight showed statistically significant change before and 24 h after surgery in the control and Isoflurane groups, but no difference in the Xylazine group. Also, the survival rate, brain infarct volume, and neurologic deficits were slightly reduced in the isoflurane group at 24 h after reperfusion injury. However, the xylazine and control groups showed similar BIV and neurologic deficits. Interestingly, a high survival rate was observed in the xylazine group. Our results indicate that the modified method of inhalation anesthetics combined with xylazine can reduce the risk of mortality and develop a reproducible MCAo model with predictable brain ischemia. In addition, extended isoflurane anesthesia after MCAo is associated with the risk of mortality.

Background: Laboratory animals remain critical to biomedical research, despite the increasing availability of alternative approaches. Indeed, scientists strive to reduce and refine and replace the use of laboratory animals, even in the face of public calls for ever-more stringent regulation for the protection and care of animals in research. This report outlines the current status and legal regulatory issues with regard to the procurement and use of animals for research in Korea.

Results: The number of animals used for education and research purposes was increased nationwide, from 2.5 to 4.9 million in 2015 and 2021, respectively. When compared with figures from the UK, institutions in Korea were found to use more mammals such as mice and dogs. In our research, we identified three major issues concerning recent animal supply in Korea, particularly: (1) Purchase of dogs from unregistered animal supplier for a dog cloning project; (2) Purchase of dogs from an unclear source for veterinary education and training; (3) Illegal cat experiments using cats obtained from unauthorized routes.

Conclusions: Our findings support the notion that alternatives to laboratory animal research should be implemented. We conclude that improvements in the regulations and guidelines for animal suppliers, together with the recent introduction of legislation will improve animal safety and wellbeing of animals in laboratory research in Korea.

Background: Enrichment of home cages in laboratory experiments offers clear advantages, but has been criticized in some respects. First, there is a lack of definition, which makes methodological uniformity difficult. Second, there is concern that the enrichment of home cages may increase the variance of results in experiments. Here, the influence of more natural housing conditions on physiological parameters of female C57BL/6J mice was investigated from an animal welfare point of view. For this purpose, the animals were kept in three different housing conditions: conventional cage housing, enriched housing and the semi naturalistic environment. The focus was on musculoskeletal changes after long-term environmental enrichment.

Results: The housing conditions had a long-term effect on the body weight of the test animals. The more complex and natural the home cage, the heavier the animals. This was associated with increased adipose deposits in the animals. There were no significant changes in muscle and bone characteristics except for single clues (femur diameter, bone resorption marker CTX-1). Additionally, the animals in the semi naturalistic environment (SNE) were found to have the fewest bone anomalies. Housing in the SNE appears to have the least effect on stress hormone concentrations. The lowest oxygen uptake was observed in enriched cage housing.

Conclusions: Despite increasing values, observed body weights were in the normal and strain-typical range. Overall, musculoskeletal parameters were slightly improved and age-related effects appear to have been attenuated. The variances in the results were not increased by more natural housing. This confirms the suitability of the applied housing conditions to ensure and increase animal welfare in laboratory experiments.

Background: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection.

Results: K18-hACE2 mice were intranasally infected with 1 × 10⁵ PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection.

Conclusion: Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.

Background: Hypertension is a medical condition that often comorbidly exist in patients with type II diabetes. Therefore, it is very important to manage both conditions simultaneously to mitigate the complications and mortality connected with this comorbidity. Hence, this study investigated the antihypertensive and antihyperglycemic effects of combinations of losartan (LOS) with metformin (MET) and/or glibenclamide (GLB) in hypertensive diabetic rats. Hypertensive diabetic state was induced with desoxycorticosterone acetate (DOCA) and streptozotocin (STZ) in adult Wistar rats. The rats were divided into 5 groups (n = 5): control group (group 1), hypertensive diabetic (HD) control (group 2), treatment groups receiving LOS + MET (group 3), LOS + GLB (group 4), and LOS + MET + GLB (group 5). Group 1 comprised healthy rats while groups 2-5 were HD rats. The rats were treated orally once daily for 8 weeks. Fasted blood glucose (FBS) level, haemodynamic parameters, and some biochemical indices were thereafter assessed.

Results: FBS level and blood pressure measurements were significantly (P < 0.05) increased following induction by DOCA/STZ. The drug treatment combinations, particularly combination of LOS + MET + GLB, significantly (P < 0.05) reduced the induced hyperglycemia and remarkably decreased systolic blood pressure and heart rate. There was significant (P < 0.05) reduction in raised lactate dehydrogenase and creatinine kinase levels by all drug treatment combinations except LOS + GLB.

Conclusions: Our findings suggest that LOS combinations with MET and/or GLB exhibited significant antidiabetic and antihypertensive effects against DOCA/STZ-induced hypertensive diabetic state in rats.

New findings in regenerative medicine have always been combined with numerous animal studies. Therefore, choosing the right translational animal model plays an important role in transferring as much basic knowledge as possible to clinical application in this field. Since microsurgery has many capabilities to perform precise interventions on small animal models and facilitates other regenerative medicine procedures, based on scientific articles, we believe that the key to the flourishing of regenerative medicine in the clinic is the use of microsurgery.

Background: Orthotopic liver transplantation is the only option for patients with end-stage liver disease and hepatocellular carcinoma. Post-transplant immunosuppressive therapy is important to prevent graft failure. We investigated the effectiveness of tacrolimus (FK506) and their mechanisms for liver transplant immune tolerance in an outbred rat LT model.

Results: To investigate the therapeutic effect of the FK506 on outbred rat LT model, FK506 and postoperative therapy were administered subcutaneously once or twice daily to transplanted rats. Histopathological and immunohistochemical analyses were conducted for all groups. The regulation of inflammatory cytokine signaling in the spleen was analyzed by flow cytometry. FK506 attenuated allograft rejection and increased survival in rat orthotopic liver transplantation models. The FK506-treated group had reduced serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. Furthermore, FK506 decreased the expression of inflammatory cytokines and the activation of pathogenic Th1 and Th17 cells in the liver.

Conclusions: Taken together, we revealed that FK506 ameliorated strong allograft rejection in outbred liver transplantation model by anti-inflammatory effect and inhibitory peroperty of pathogenic T cells.

Background: Cudrania tricuspidata is a perennial plant, and Sargassum fusiforme is a brown seaweed with numerous potential benefits, including anticancer, anti-inflammatory, and antioxidant activities. However, the efficacies of C. tricuspidata and S. fusiforme on hair growth have not yet been elucidated. Therefore, the present study examined the effects of C. tricuspidata and S. fusiforme extracts on hair growth in C57BL/6 mice.

Results: ImageJ demonstrated that drinking and skin application of C. tricuspidata and/or S. fusiforme extracts significantly increased the hair growth rate in the dorsal skin of C57BL/6 mice compared to the control group. Histological analysis confirmed that drinking and skin application of C. tricuspidata and/or S. fusiforme extracts for 21 days significantly increased the length of hair follicles on the dorsal skin of treated C57BL/6 mice compared to that in the control mice. RNA sequencing analysis revealed that hair growth cycle-related factors (anagen factors) such as Catenin Beta 1 (Ctnnb1) and platelet-derived growth factor (Pdgf) were upregulated (> twofold) only by C. tricuspidate extracts, whereas vascular endothelial growth factor (Vegf) and Wnts were upregulated by both C. tricuspidata or S. fusiforme applications in treated mice (compared to the control mice). In addition, oncostatin M (Osm, a catagen-telogen factor) was downregulated (< 0.5 fold) by C. tricuspidata when administered via both skin and drinking mode in treated mice compared to that in control mice.

Conclusions: Our results suggest that C. tricuspidata and/or S. fusiforme extracts show potential hair growth efficacy by upregulating anagen factor genes, including β-catenin, Pdgf, Vegf, and Wnts, and downregulating catagen-telogen factor genes, including Osm, in C57BL/6 mice. The findings suggest that C. tricuspidata and/or S. fusiforme extracts are potential drug candidates to treat alopecia.