Pub Date : 2025-09-24DOI: 10.1038/s41684-025-01601-9
Omar A. Selim, Aida Sarcon, Mehmet Tunaboylu, Chunfeng Zhao, Steven L. Moran
Rhabdomyolysis following revascularization of the ischemic upper extremity can lead to life- and limb-threatening sequelae. In the context of replantations and vascularized composite allografting, a reconstructive procedure usually reserved for upper limb amputees, prolonged tissue ischemia is detrimental to extremity functional recovery. Currently, validated survival small animal models of extremity reperfusion injury that permit longitudinal assessment of limb function are lacking. So far, studies that evaluated reperfusion injury-induced neuromuscular impairment have relied on terminal ex vivo procedures and did not provide clinically translatable measurements. Here we present a reliable rat model of extremity post-reperfusion syndrome (PRS) that comprehensively recapitulates the biochemical hallmarks of rhabdomyolysis secondary to upper-extremity reperfusion injury and allows the monitoring of in vivo upper limb function using clinically relevant electrodiagnostic and kinematic metrics. In addition to inducing severe metabolic derangements, our forelimb PRS model provided insights on gross motor and electrophysiological alterations following upper-extremity reperfusion injury. We identify gait coordination parameters—such as stride frequency and the forelimb–hindlimb coordination index—and electrophysiological metrics, including compound muscle action potential amplitude, as objective and noninvasive outcome measures for assessing limb function in small animal models of extremity PRS. This comprehensive, validated functional model can serve as an invaluable tool to evaluate therapeutics or preconditioning regimens to attenuate PRS and mitigate resulting neuromuscular dysfunction. The authors report the development of a new rat model of forelimb ischemia–reperfusion injury, characterized by motor coordination deficits, impairment of neuromuscular transmission and serum biochemical and inflammatory changes.
{"title":"A longitudinal rat forelimb model for assessing in vivo neuromuscular function following extremity reperfusion injury","authors":"Omar A. Selim, Aida Sarcon, Mehmet Tunaboylu, Chunfeng Zhao, Steven L. Moran","doi":"10.1038/s41684-025-01601-9","DOIUrl":"10.1038/s41684-025-01601-9","url":null,"abstract":"Rhabdomyolysis following revascularization of the ischemic upper extremity can lead to life- and limb-threatening sequelae. In the context of replantations and vascularized composite allografting, a reconstructive procedure usually reserved for upper limb amputees, prolonged tissue ischemia is detrimental to extremity functional recovery. Currently, validated survival small animal models of extremity reperfusion injury that permit longitudinal assessment of limb function are lacking. So far, studies that evaluated reperfusion injury-induced neuromuscular impairment have relied on terminal ex vivo procedures and did not provide clinically translatable measurements. Here we present a reliable rat model of extremity post-reperfusion syndrome (PRS) that comprehensively recapitulates the biochemical hallmarks of rhabdomyolysis secondary to upper-extremity reperfusion injury and allows the monitoring of in vivo upper limb function using clinically relevant electrodiagnostic and kinematic metrics. In addition to inducing severe metabolic derangements, our forelimb PRS model provided insights on gross motor and electrophysiological alterations following upper-extremity reperfusion injury. We identify gait coordination parameters—such as stride frequency and the forelimb–hindlimb coordination index—and electrophysiological metrics, including compound muscle action potential amplitude, as objective and noninvasive outcome measures for assessing limb function in small animal models of extremity PRS. This comprehensive, validated functional model can serve as an invaluable tool to evaluate therapeutics or preconditioning regimens to attenuate PRS and mitigate resulting neuromuscular dysfunction. The authors report the development of a new rat model of forelimb ischemia–reperfusion injury, characterized by motor coordination deficits, impairment of neuromuscular transmission and serum biochemical and inflammatory changes.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 10","pages":"259-269"},"PeriodicalIF":3.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anesthesia is indispensable for minimizing stress during invasive procedures. However, anesthesia can induce undesired effects on the organism and its physiological homeostasis. In experiments involving animals, these consequences may reduce animal welfare and alter experimental outcomes. Moreover, most of the studies characterizing the effects of murine anesthetic protocols on animal welfare do not explore the impact of prolonged anesthesia for procedures lasting more than 2 h. Here we investigated the effect of prolonged anesthesia on vital parameters and immune responses to vaccination, comparing isoflurane (Iso), ketamine–xylazine (KX), and KX with oxygen supplementation (KXO2), in the presence or absence of buprenorphine (BPP). KX induced hypoxia and 100% mortality, which were prevented by oxygen supplementation (KXO2) and were not associated with BPP. By contrast, Iso induced safe and fast induction and recovery. Furthermore, we investigated the effects of these protocols on the immune responses and motility of immune cells following vaccination. The results showed that KX reduced immune cell numbers and increased cell death, complemented by elevated levels of the inflammatory proteins IL-6 and IFNγ. In addition, KX altered the motility patterns of T cells, B cells and neutrophils, potentially influenced by hypoxia. Conversely, Iso exhibited fewer immune artifacts, regardless of BPP. These findings highlight the importance of evaluating anesthesia protocols with respect to animal welfare and experimental reproducibility, especially for immunological studies. Oxygen supplementation emerged as an important refinement to mitigate hypoxia in KX. Iso showed superior safety and fewer artifacts compared with KX and KXO2, demonstrating its suitability for immunological research and intravital microscopy. The study reveals that long-term anesthesia with ketamine–xylazine can induce hypoxia and mortality in mice, whereas oxygen supplementation mitigates these effects. As an alternative, isoflurane showed superior safety and fewer effects on the immune system.
{"title":"Impact of prolonged isoflurane or ketamine–xylazine anesthesia with or without buprenorphine and oxygen on mouse vitals and immune responses","authors":"Tommaso Virgilio, Irene Latino, Chiara Pizzichetti, Kamil Chahine, Arianna Capucetti, Carlotta Detotto, Alessandra Bergadano, Santiago F.Gonzalez","doi":"10.1038/s41684-025-01614-4","DOIUrl":"10.1038/s41684-025-01614-4","url":null,"abstract":"Anesthesia is indispensable for minimizing stress during invasive procedures. However, anesthesia can induce undesired effects on the organism and its physiological homeostasis. In experiments involving animals, these consequences may reduce animal welfare and alter experimental outcomes. Moreover, most of the studies characterizing the effects of murine anesthetic protocols on animal welfare do not explore the impact of prolonged anesthesia for procedures lasting more than 2 h. Here we investigated the effect of prolonged anesthesia on vital parameters and immune responses to vaccination, comparing isoflurane (Iso), ketamine–xylazine (KX), and KX with oxygen supplementation (KXO2), in the presence or absence of buprenorphine (BPP). KX induced hypoxia and 100% mortality, which were prevented by oxygen supplementation (KXO2) and were not associated with BPP. By contrast, Iso induced safe and fast induction and recovery. Furthermore, we investigated the effects of these protocols on the immune responses and motility of immune cells following vaccination. The results showed that KX reduced immune cell numbers and increased cell death, complemented by elevated levels of the inflammatory proteins IL-6 and IFNγ. In addition, KX altered the motility patterns of T cells, B cells and neutrophils, potentially influenced by hypoxia. Conversely, Iso exhibited fewer immune artifacts, regardless of BPP. These findings highlight the importance of evaluating anesthesia protocols with respect to animal welfare and experimental reproducibility, especially for immunological studies. Oxygen supplementation emerged as an important refinement to mitigate hypoxia in KX. Iso showed superior safety and fewer artifacts compared with KX and KXO2, demonstrating its suitability for immunological research and intravital microscopy. The study reveals that long-term anesthesia with ketamine–xylazine can induce hypoxia and mortality in mice, whereas oxygen supplementation mitigates these effects. As an alternative, isoflurane showed superior safety and fewer effects on the immune system.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 10","pages":"270-277"},"PeriodicalIF":3.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41684-025-01614-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 : 2025-08-25DOI: 10.1038/s41684-025-01606-4
Alexandra Le Bras
{"title":"A pig model of Angelman syndrome","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01606-4","DOIUrl":"10.1038/s41684-025-01606-4","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 9","pages":"223-223"},"PeriodicalIF":3.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1038/s41684-025-01607-3
Jorge Ferreira
{"title":"Channeling male aggression to other behaviors","authors":"Jorge Ferreira","doi":"10.1038/s41684-025-01607-3","DOIUrl":"10.1038/s41684-025-01607-3","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 9","pages":"224-224"},"PeriodicalIF":3.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1038/s41684-025-01610-8
Jorge Ferreira
{"title":"Lymphatic system role in ALS","authors":"Jorge Ferreira","doi":"10.1038/s41684-025-01610-8","DOIUrl":"10.1038/s41684-025-01610-8","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 9","pages":"224-224"},"PeriodicalIF":3.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1038/s41684-025-01609-1
Jorge Ferreira
{"title":"Drosophila functional model of atrial fibrillation","authors":"Jorge Ferreira","doi":"10.1038/s41684-025-01609-1","DOIUrl":"10.1038/s41684-025-01609-1","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 9","pages":"224-224"},"PeriodicalIF":3.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1038/s41684-025-01602-8
Michael J. Hurley, B. Maximiliano Garduño, Robert M. J. Deacon, Todd C. Holmes, Xiangmin Xu, Patricia Cogram
The study of aging and age-related diseases has traditionally focused on short-lived laboratory species such as mice. The common degu (Octodon degus) is a long-lived rodent species native to Chile that naturally develops neuropathology and behavioral deficits characteristic of Alzheimer’s disease together with other comorbidities associated with aging. These characteristics make the degu a useful model to gain insights into the interaction of aging and neurodegeneration.
{"title":"Octodon degus: a natural animal model of aging and Alzheimer’s disease","authors":"Michael J. Hurley, B. Maximiliano Garduño, Robert M. J. Deacon, Todd C. Holmes, Xiangmin Xu, Patricia Cogram","doi":"10.1038/s41684-025-01602-8","DOIUrl":"10.1038/s41684-025-01602-8","url":null,"abstract":"The study of aging and age-related diseases has traditionally focused on short-lived laboratory species such as mice. The common degu (Octodon degus) is a long-lived rodent species native to Chile that naturally develops neuropathology and behavioral deficits characteristic of Alzheimer’s disease together with other comorbidities associated with aging. These characteristics make the degu a useful model to gain insights into the interaction of aging and neurodegeneration.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 9","pages":"219-222"},"PeriodicalIF":3.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41684-025-01602-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 : 2025-08-25DOI: 10.1038/s41684-025-01605-5
Alexandra Le Bras
{"title":"Long-term impact of SARS-CoV-2 infection in hamsters","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01605-5","DOIUrl":"10.1038/s41684-025-01605-5","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 9","pages":"223-223"},"PeriodicalIF":3.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1038/s41684-025-01604-6
Alexandra Le Bras
{"title":"A gastropod model of eye regeneration","authors":"Alexandra Le Bras","doi":"10.1038/s41684-025-01604-6","DOIUrl":"10.1038/s41684-025-01604-6","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 9","pages":"223-223"},"PeriodicalIF":3.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144900199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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