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+ 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.
{"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}
Pub Date : 2025-01-10Epub Date: 2024-08-08DOI: 10.1538/expanim.24-0027
Xiaolong Zhao, Longqi Shang, Chunjian Shen
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.
{"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}
Pub Date : 2025-01-10Epub Date: 2024-08-08DOI: 10.1538/expanim.24-0036
Wei-Mao Hung, Hsien-Chi Wang, Julia Chu-Ning Hsu
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.
{"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}