{"title":"Inhibition of tumor necrosis factor receptor-associated factor 6 alleviates secondary brain injury by reducing neuronal pyroptosis after intracerebral hemorrhage.","authors":"Qianxin Hu, Haixin Zeng, Chengao Feng, Wei Tian, Yuxin He, Bing Li","doi":"10.1538/expanim.24-0078","DOIUrl":"10.1538/expanim.24-0078","url":null,"abstract":"<p><p>Secondary brain injury (SBI) is one of the main causes of high mortality and disability rates following intracerebral hemorrhage (ICH). Tumor necrosis factor receptor-associated factor 6 (TRAF6) plays a crucial role in the process of pyroptosis, and modulating its expression may present a novel therapeutic strategy for mitigating brain injury. This study aims to explore the mechanisms of TRAF6 in pyroptosis after ICH. C57BL/6J mice were used to establish the ICH model. Brain was collected at different time points for q-PCR and western blot to detect the level of TRAF6. After the C25-140 (the TRAF6 inhibitor) was administrated, the mice were divided into four groups. Then, the neurological deficit, brain water content, and blood-brain barrier (BBB) damage were detected. Immunofluorescence and western blot were used to detect the level of pyroptosis proteins, and ELISA and q-PCR were used to detect the levels of IL-18 and IL-1β. TRAF6 expression was upregulated after ICH and was mainly expressed in neurons. Inhibition of TRAF6 expression with C25-140 alleviated neurological deficits and reduced brain edema after ICH. In addition, inhibition of TRAF6 also reduced the expression of pyroptosis inflammasomes such as GSDMD, NLRP3, and ASC, as well as neurological damage caused by IL-18 and IL-1β after ICH. TRAF6 regulates neuronal pyroptosis in SBI after ICH. Inhibition of TRAF6 may be a potential target for alleviating inflammatory damage after ICH.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"39-48"},"PeriodicalIF":2.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endothelial GATA3 is involved in coagulofibrinolytic homeostasis during endotoxin sepsis.","authors":"Moyuru Hayashi, Shin'ya Ohmori, Yoshiko Kawai, Takashi Moriguchi","doi":"10.1538/expanim.24-0079","DOIUrl":"10.1538/expanim.24-0079","url":null,"abstract":"<p><p>Sepsis-induced acute lung injury represents a significant threat to human health and is frequently associated with pulmonary thrombosis due to dysregulation of the coagulofibrinolytic system. Plasmin, the major protease that degrades fibrin aggregates, is activated predominantly by tissue-plasminogen activator (tPA), whereas tPA is negatively regulated by plasminogen activator inhibitor (PAI-1). Under septic conditions, the imbalance between coagulation and fibrinolysis results in excessive microthrombosis. Pulmonary capillary endothelial cells serve as a primary source of tPA and PAI-1. The molecular pathways regulating their expression levels depend on the differential activity of transcription factors. In this study, we elucidated the role of the zinc-finger transcription factor GATA3 in response to sepsis-induced pulmonary embolism. Endothelial cell-specific GATA3-deficient mice (G3-ECKO) presented increased susceptibility to bacterial endotoxin-induced pulmonary embolism, which was associated with increased PAI-1 expression levels and decreased tPA expression levels in the lungs. Septic lung extracts from G3-ECKO mice consistently presented decreased plasmin activity, which likely underlies the increased coagulation. These results demonstrate that GATA3 plays a protective role against bacterial endotoxin-induced pulmonary vascular embolism. Our findings will contribute to understanding the molecular mechanisms involving GATA3 in preventing pulmonary embolism.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"104-113"},"PeriodicalIF":2.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of gene mutations associated with the phenotype of short-limb mice emerging from a foundation colony of severely immunodeficient mice.","authors":"Yui Kaneko, Kayo Tomiyama, Masahiko Yasuda, Yuji Komaki, Tomoyuki Ogura, Riichi Takahashi, Masafumi Yamamoto","doi":"10.1538/expanim.24-0045","DOIUrl":"10.1538/expanim.24-0045","url":null,"abstract":"<p><p>Here, we report the identification of causative genes for limb-shortening in individuals repeatedly found in a population of severely immunodeficient NOG mice maintained via sibling mating. First, we conducted a pedigree survey to determine whether limb-shortening was a recessive genetic trait and then identified it using a crossing test. Simultaneously, the symptoms were identified in detail using pathological analysis. Accordingly, a mouse strain exhibiting a recessive trait caused by a single gene trait and similar symptoms was identified, suggesting growth differentiation factor 5 (Gdf5) as a causative gene. Genome walking via PCR and sequence analysis of Gdf5 revealed a deletion of approximately 1.1 kb from the latter half of exon 2 of Gdf5. Furthermore, we established NOG-Gdf5<sup>bpJic</sup> by removing other modified genes and confirmed that the inheritance pattern was reconfirmed semi-dominant. In recent years, regenerative medicine research using immunodeficient mice has been actively conducted, and this murine strain is expected to contribute to niche stem cell analysis and transplantation research.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"122-131"},"PeriodicalIF":2.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2025-01-10Epub Date: 2024-08-28DOI: 10.1538/expanim.24-0029
Xiaoqi Chang, Jiping Gao, Junting Yang, Yunhui Ma, Guohua Song
{"title":"The Chinese hamster as an excellent experimental animal model.","authors":"Xiaoqi Chang, Jiping Gao, Junting Yang, Yunhui Ma, Guohua Song","doi":"10.1538/expanim.24-0029","DOIUrl":"10.1538/expanim.24-0029","url":null,"abstract":"<p><p>Hamsters are valuable rodent models that are distinct from mice and rats. Currently, the main hamster species used for experimental research are the Syrian golden hamster and Chinese hamster, in addition to hamster species from other countries. Chinese hamsters are small, easy to run and feed, and inexpensive. They are prominent species found only in China and are part of the experimental animal resources of Chinese specialty. Chinese hamsters are distinguished by a black stripe on their back, short tail, pair of easily retractable cheek pouches, and pair of large drooping testes in males with 22 chromosomes. Due to their unique anatomical structure and biological features, Chinese hamsters have been used as a model in biomedical research. Moreover, the breeding and use of Chinese hamsters was comprehensively studied in 1958, with significant breakthroughs. We present a thorough review of the current developments and applications of Chinese hamsters and support the use of this species as a suitable and innovative experimental research model. With the success of Chinese hamster transgenic technology, this species will become more commonly employed in biological and medical research in the future.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"1-15"},"PeriodicalIF":2.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2025-01-10Epub Date: 2024-09-07DOI: 10.1538/expanim.24-0050
Mao Sato, Chiaki Sugiura, Nobuaki Okumura, Akira Terao
{"title":"Melinjo (Gnetum gnemon L.) seed extract for treatment of sleep/wake fragmentation in diet-induced obese mice.","authors":"Mao Sato, Chiaki Sugiura, Nobuaki Okumura, Akira Terao","doi":"10.1538/expanim.24-0050","DOIUrl":"10.1538/expanim.24-0050","url":null,"abstract":"<p><p>Dietary supplementation with melinjo (Gnetum gnemon L.) seed extract (MSE) has been an integral part of an anti-obesity therapeutic regimen. To examine the relationship between anti-obesity and sleep, we explored the effect of MSE on sleep structure in high-fat diet (HFD)-induced obese mice. Although HFD did not alter the total amount of daily sleep, it significantly reduced the average duration of non-rapid eye movement (NREM) sleep and wakefulness episodes and significantly increased the number of these episodes. These findings indicate fragmented NREM sleep due to repeated brief awakenings in the HFD-fed mice. When 1% (w/v) MSE was given to HFD-fed mice, their weight or sleep structure were comparable to those of ND-fed mice, proving that dietary MSE completely hindered HFD-induced weight gain and sleep/wake fragmentation. Our data provide compelling evidence that MSE is a novel and promising dietary supplement that restores obesity-induced sleep architecture changes in mice.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"114-121"},"PeriodicalIF":2.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Clodronate liposome treatment contributes to the nerve regeneration in corneal nerve involvement of diabetic mice.","authors":"Hiroki Ueno, Takaaki Hattori, Hsi-Hua Chi, Yoshishige Miyabe, Masanori A Murayama","doi":"10.1538/expanim.24-0063","DOIUrl":"10.1538/expanim.24-0063","url":null,"abstract":"<p><p>The dense nerve and thin vascular structure of the corneal tissue provide the refractive function in healthy eyes. Diabetes mellitus causes ocular complications including corneal opacification because of corneal nerve degeneration. Diabetic neurotrophic keratopathy is characterized by reduced corneal sensitivity, delayed corneal wound healing, and nerve degeneration. Neurotization and vascularization inhibit each other in the cornea. Macrophages contribute to the corneal neovascularization. To investigate the role of macrophage in neurotrophic keratopathy, clodronate liposome was subconjunctivally injected into diabetic db/db mice with neurotrophic keratopathy. The clodronate liposome treatment decreased F4/80<sup>+</sup> macrophage infiltration into the corneal epithelium, and improved corneal nerve involvement in diabetic db/db mice. Furthermore, we found that Il1b and Il34 mRNA expression was increased in the corneal epithelium of clodronate-treated diabetic db/db mice. These cytokines contribute to the maintenance of nerve tissues via microglia and nerve regeneration; however, their role in corneal nerve involvement remains unknown. Notably, the intraocular injection of recombinant IL-1β and IL-34 promoted nerve regeneration in the cornea of diabetic db/db mice. These results suggest that clodronate liposome treatment contributes to nerve regeneration during corneal involvement via IL-1β and IL-34 signaling.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"58-65"},"PeriodicalIF":2.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2025-01-10Epub Date: 2024-08-08DOI: 10.1538/expanim.24-0027
Xiaolong Zhao, Longqi Shang, Chunjian Shen
{"title":"Daphnetin ameliorates diabetic cardiomyopathy by regulating inflammation and endoplasmic reticulum stress-induced apoptosis.","authors":"Xiaolong Zhao, Longqi Shang, Chunjian Shen","doi":"10.1538/expanim.24-0027","DOIUrl":"10.1538/expanim.24-0027","url":null,"abstract":"<p><p>Daphnetin has been demonstrated to exert beneficial effects on diabetes mellitus and renal complications. However, the role and molecular mechanism of daphnetin in diabetic cardiomyopathy (DCM) remain unclear. In this study, rats were injected with streptozotocin (STZ) to induce diabetes. The diabetic rats were then administered daphnetin (1 and 4 mg/kg) or dimethyl sulfoxide (DMSO) daily for 12 weeks. The results demonstrated that the diabetic rats exhibited elevated blood glucose levels, which were dose-dependently ameliorated by daphnetin. At 13 weeks following STZ injection, the rats exhibited typical diabetic signs, cardiac dysfunction, and evident pathological alterations in myocardial tissues. The administration of daphnetin to diabetic rats resulted in improvement in cardiac function, reductions in myocardial injury biomarkers, and the inhibition of myocardial fibrosis. Furthermore, daphnetin treatment suppressed inflammation and endoplasmic reticulum stress-induced apoptosis in a dose-dependent manner. Additionally, daphnetin exhibited partial blockade of the activation of mitogen-activated protein kinase pathways induced by diabetes. These findings indicate that daphnetin may be a promising therapeutic agent for the treatment of DCM.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"49-57"},"PeriodicalIF":2.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Experimental AnimalsPub Date : 2025-01-10Epub Date: 2024-08-08DOI: 10.1538/expanim.24-0036
Wei-Mao Hung, Hsien-Chi Wang, Julia Chu-Ning Hsu
{"title":"A novel electroencephalographic evaluation of noxious stimulation during isoflurane anesthesia in dogs.","authors":"Wei-Mao Hung, Hsien-Chi Wang, Julia Chu-Ning Hsu","doi":"10.1538/expanim.24-0036","DOIUrl":"10.1538/expanim.24-0036","url":null,"abstract":"<p><p>In veterinary clinical medicine, evaluating the balance between nociception and antinociception presents a great challenge for anesthesiologists during canine surgeries. Heart rate (HR) and mean arterial pressure (MAP) are suitable indexes for monitoring noxious stimuli during anesthesia. Frontal electroencephalography (EEG) records, including processed parameters, are recommended for evaluating nociceptive balance in anesthetized unconscious human patients, which is unexplored in veterinary medicine. Therefore, the objective is to explore the response of processed EEG parameters to noxious stimulation and elucidate the impact of noxious stimulation on frontal cortical activity in dogs anesthetized with 1.5% isoflurane. Fourteen dogs were included and underwent frontal EEG monitoring, measuring the patient state index (PSI) and spectral edge frequency (SEF) before and after administering noxious stimulation using the towel clamp method on the tail of each 1.5% isoflurane-anesthetized dog. As the noxious stimulation was applied, there was a simultaneous increase in PSI, HR, and MAP, with PSI exhibiting a drastic response. SEF, especially on the left side, also increased with noxious stimulation. In EEG power spectral analysis, the delta band was decreased, and the alpha and beta bands showed an increase following noxious stimulation, with a more profound elevation of beta band on the left side. This study suggests that noxious stimulation brings asymmetric frontal cortical arousal, changing brain activity by suppressing delta wave and augmenting alpha and beta waves. Consequently, PSI seems to be a potential indicator for detecting stimuli in canine isoflurane anesthesia.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":" ","pages":"83-92"},"PeriodicalIF":2.2,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}