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Rabbit, a member of the Lagomorpha order, is the closest phylogenetic relative to humans, next to primates. It possesses greater acceptability as a laboratory mammal than primates in terms of husbandry, breeding ease, cost effectiveness, and legal ethical conveniences. Moreover, as a laboratory animal, the rabbit also owns its advantages over mice...
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... Case descriptions including age, sex, breed, body weight, and tumor location were also recorded. The rabbits' age ranges were classified into four groups based on their life stages: young adult (1-3 years), middle age (>3-5 years), late middle age (>5-6 years), and old age (>6-10 years) [12]. ...
Rabbit oncology is gaining more attention as more pet rabbits are surviving beyond their normal lifespans. Due to the limited epidemiological information on pet rabbits’ tumors in Thailand, this study aimed to report the prevalence and the potential risk factors associated with tumors in pet rabbits in Thailand. From 2018 to 2022, 93 tissue biopsies from tumor-suspected lesions on pet rabbits were gathered from animal hospitals in Bangkok and Chonburi provinces, Thailand. According to histopathology confirmation, tumors and tumor-like lesions were diagnosed. In this study, the overall tumors were 67.74% (n=63) out of the submitted cases (n=93). The most commonly affected organ systems were reproduction (65.08%) and integumentary (22.22%). Rabbits older than 5 years were 3.85 times more likely to have reproductive tumors than younger rabbits (95% confidence interval (CI): 1.45–10.27, P-value ≤0.01), and the most frequently occurring tumor type was uterine adenocarcinoma. Furthermore, male rabbits had a 17.02 times higher probability of developing cutaneous tumors than female rabbits (95% CI: 4.19–69.11, P-value ≤0.001), and the most frequently occurring tumor type was soft tissue sarcoma. The results of this study thus suggested that the age and sex of the rabbits were potential risk factors for tumor development in Thailand. The knowledge gained from our study also provided the recommendation for owners to monitor their rabbits’ health annually, particularly after late middle age, and rendered guidance for tumor detection in practical clinics.
... Currently, there are few approaches to compare the lifespan of diverse species (for an approach for rabbits and humans, see [17]), and most comparative aging studies focus on related species groups (e.g. [18,19]). ...
Comparative studies of aging are a promising approach to identifying general properties of and processes leading to aging. While to date, many comparative studies of aging in animals have focused on relatively narrow species groups, methodological innovations now allow for studies that include evolutionary distant species. However, comparative studies of aging across a wide range of species that have distinct life histories introduce additional challenges in experimental design. Here, we discuss these challenges, highlight the most pressing problems that need to be solved, and provide suggestions based on current approaches to successfully carry out comparative aging studies across the animal kingdom.
... In addition, they possess advantages over mice or rats in terms of evolutionary similarity to humans in blood volume, responsiveness and other resemblance. Further, they are considered superior laboratory animals, since they may closely mimic human physiological traits in biomedical research [45]. The edentulous space between the incisors and premolars was selected to be the experimental site because during mastication, this region is most likely to experience mechanical stress. ...
Biomaterials such as chitosan and simvastatin (Sim) have been introduced to accelerate the extensive and multicellular biological process of bone healing. The aim of this study was to evaluate the bone healing potential of chitosan and Sim, alone or combined. Forty-two male New Zealand rabbits were divided into three groups: chitosan nanoparticles (ChN), Sim and chitosan simvastatin nanoparticles (ChSimN). Two bony defects were created in the maxillary bone. The hole on the right side received one of the experimental materials, while the other side was assigned as the control and left to heal without any intervention. Bone specimens were collected at 2 and 4 weeks and then taken for histological and histomorphometrical analyses. The histological findings revealed that ChN possessed the highest number of osteoblasts and osteoclasts at weeks 2 and osteocytes after 4 weeks. There was a significant difference between the two healing periods regarding all bone parameters across all groups. ChN stood out as the only group that had a significant difference in the count of all bone cells between the two periods, thus having the best potential in promoting bone healing.
... Using body weight at arrival and according to the growth rate for New Zealand White rabbits [38], age was estimated and then scaled to that of humans according to the duration of different phases of life [39] (Figure 1). Temporal hemodynamic and morphological evaluation was performed as a function of age using Doppler ultrasound imaging following protocols similar to human transthoracic echocardiography. ...
... Lastly, the thickness evolution was normalized to interpolated body weights at each timepoint assuming scaling of the body weight according to a sigmoid function ( Figure 3). The sigmoid function was selected specifically to allow for a relatively low initial growth rate during the gestation period (~32 days) assuming an average of 50 g for newborn rabbit weight [39], as well as stable body weight, upon reaching adulthood. Doppler ultrasound follow-up was performed weekly to quantify the temporal evolution of hemodynamic changes (A, spectral Doppler) and morphology (B, Doppler b-mode) in response to the CoA. ...
... Lastly, the thickness evolution was normalized to interpolated body weights at each timepoint assuming scaling of the body weight according to a sigmoid function ( Figure 3). The sigmoid function was selected specifically to allow for a relatively low initial growth rate during the gestation period (~32 days) assuming an average of 50 g for newborn rabbit weight [39], as well as stable body weight, upon reaching adulthood. . Representative thickness and body weight evolution over time for a CoA rabbit. ...
Background: Coarctation of the aorta (CoA; constriction of the proximal descending thoracic aorta) is among the most common congenital cardiovascular defects. Coarctation-induced mechanical perturbations trigger a cycle of mechano-transduction events leading to irreversible precursors of hypertension including arterial thickening, stiffening, and vasoactive dysfunction in proximal conduit arteries. This study sought to identify kinetics of the stress-mediated compensatory response leading to these alterations using a preclinical rabbit model of CoA. Methods: A prior growth and remodeling (G&R) framework was reformulated and fit to empirical measurements from CoA rabbits classified into one control and nine CoA groups of various severities and durations (n = 63, 5–11/group). Empirical measurements included Doppler ultrasound imaging, uniaxial extension testing, catheter-based blood pressure, and wire myography, yielding the time evolution of arterial thickening, stiffening, and vasoactive dysfunction required to fit G&R constitutive parameters. Results: Excellent agreement was observed between model predictions and observed patterns of arterial thickening, stiffening, and dysfunction among all CoA groups. For example, predicted vascular impairment was not significantly different from empirical observations via wire myography (p-value > 0.13). Specifically, 48% and 45% impairment was observed in smooth muscle contraction and endothelial-dependent relaxation, respectively, which were accurately predicted using the G&R model. Conclusions: The resulting G&R model, for the first time, allows for prediction of hypertension precursors at neonatal ages that is currently challenging to examine in preclinical models. These findings provide a validated computational tool for prediction of persistent arterial dysfunction and identification of revised severity–duration thresholds that may ultimately avoid hypertension from CoA.
... The lifespan is undoubtedly different between rabbits and humans. Figure 5 provides guidance relating time points from the current study to the human lifespan 52 . The collective application of these findings suggests our results may be applicable to other species (i.e. ...
Coarctation of the aorta (CoA) is one of the most common congenital cardiovascular diseases. CoA patients frequently undergo surgical repair, but hypertension (HTN) is still common. The current treatment guideline has revealed irreversible changes in structure and function, yet revised severity guidelines have not been proposed. Our objective was to quantify temporal alterations in mechanical stimuli and changes in arterial geometry in response to the range of CoA severities and durations (i.e. age of treatment) seen clinically. Rabbits were exposed to CoA resulting in peak-to-peak blood pressure gradient (BPGpp) severities of ≤ 10, 10–20, and ≥ 20 mmHg for a duration of ~ 1, 3, or 20 weeks using permanent, dissolvable, and rapidly dissolvable sutures. Elastic moduli and thickness were estimated from imaging and longitudinal fluid–structure interaction (FSI) simulations were conducted at different ages using geometries and boundary conditions from experimentally measured data. Mechanical stimuli were characterized including blood flow velocity patterns, wall tension, and radial strain. Experimental results show vascular alternations including thickening and stiffening proximal to the coarctation with increasing severity and/or duration of CoA. FSI simulations indicate wall tension in the proximal region increases markedly with coarctation severity. Importantly, even mild CoA induced stimuli for remodeling that exceeds values seen in adulthood if not treated early and using a BPGpp lower than the current clinical threshold. The findings are aligned with observations from other species and provide some guidance for the values of mechanical stimuli that could be used to predict the likelihood of HTN in human patients with CoA.
... Phylogenetically, rabbits are the next closest relative to primates. Moreover, compared to mice and rats, rabbits share more similar physiological characteristics with humans [26]. Recently, we reported that healthy rabbits are susceptible to EBV infection, and the infection resembles what is observed in humans [27]. ...
Epstein–Barr virus (EBV) is etiologically associated with a number of malignant and non-malignant conditions. Thus, a prophylactic vaccine against this virus could help to reduce the burden of many EBV-associated diseases. Previously, we reported that an EBV virus-like particle (VLP) vaccine was highly immunogenic and produced a strong humoral response in mice. However, since EBV does not infect mice, the efficacy of the VLP in preventing EBV infection could not be addressed. Here we examined, for the first time, the efficacy of the EBV-VLP vaccine using a novel rabbit model of EBV infection. Animals vaccinated with two doses of VLP elicited higher antibody responses to total EBV antigens compared to animals receiving one dose. Vaccinated animals also elicited both IgM and IgG to EBV-specific antigens, VCA and EBNA1. Analysis of peripheral blood and spleen for EBV copy number indicated that the viral load in both of these compartments was lower in animals receiving a 2-dose vaccine. However, the VLP vaccine was ineffective in preventing EBV infection. With several other EBV vaccine candidates currently at various stages of development and testing, we believe that the rabbit model of EBV infection could be a great platform for evaluating potential candidates.
... The following data extracted from the clinical record of all the rabbits cared for during the established study period were recorded: record number, sex (male/female), age (measured in months), age was later categorized in newborn (up to 3 months), juveniles (from 3 to 12 months), adults (from 12 months to 7 years), and seniors (more than 7 years) considering prior information [17], weight (grams), body condition (BCS) (scale 1/5) [18], breed (dwarf/medium/large) based on previous data [17,19,20] (Table S1), reproductive status (neutered/intact), type of housing (caged/free range pets/mixed), housing regimen (indoor/outdoor/mixed), consumption of hay (yes/no), consumption of vegetables (yes/no), consumption of fruit (yes/no), consumption of pellets (yes/no), diagnostic imaging (includes radiography and/or CT; yes /no), and clinical signs. ...
... The following data extracted from the clinical record of all the rabbits cared for during the established study period were recorded: record number, sex (male/female), age (measured in months), age was later categorized in newborn (up to 3 months), juveniles (from 3 to 12 months), adults (from 12 months to 7 years), and seniors (more than 7 years) considering prior information [17], weight (grams), body condition (BCS) (scale 1/5) [18], breed (dwarf/medium/large) based on previous data [17,19,20] (Table S1), reproductive status (neutered/intact), type of housing (caged/free range pets/mixed), housing regimen (indoor/outdoor/mixed), consumption of hay (yes/no), consumption of vegetables (yes/no), consumption of fruit (yes/no), consumption of pellets (yes/no), diagnostic imaging (includes radiography and/or CT; yes /no), and clinical signs. ...
Simple Summary
There has been an increase in domestic rabbit ownership in the recent years. The type of dentition of this exotic (non-traditional) animal pet, predisposes it to the development of Acquired Dental Disease (ADD), a disease that affects tooth quality, generates malocclusion, among other dental and non-dental consequences. The aim of this study was to assess the factors that modify the risk for ADD in domestic pet rabbits. For this, 1420 owned rabbits’ clinical records from a private practice from 2018 to 2021 were used, recording several variables, including the clinical signs at diagnosis. ADD was detected in 25.4% of the individuals, mostly on their cheek teeth. In addition, age and sex (male) were found to be significant risk factors for ADD. In contrast, a free lifestyle and consuming hay in the diet were protective factors. Understanding the factors that modify the risk of ADD increases the chances of prevention and helps to improve the education of owners and/or guardians of domestic rabbits.
Abstract
Rabbits (Oryctolagus cuniculus) have elodont dentition, a characteristic that predisposes them to the development of Acquired Dental Disease (ADD), which is a multifactorial disease. The aim of this study was to assess the risk factors for ADD in domestic pet rabbits. To do this, a retrospective analysis of 1420 rabbits treated at a private practice during 2018–2021 was performed. For this, several variables were retrieved from clinical records, in addition to signology at the time of diagnosis. ADD was found on 25.4% of rabbits, mostly on their cheek teeth. In addition, age (OR = 1.029; 95% CI = 1.023–1.035; p < 0.001) and sex (male) (OR = 1.591; 95% CI = 1.226–2.064; p < 0.001) were found to be significant risk factors for ADD. In contrast, a free lifestyle (OR = 0.565; 95% CI = 0.362–0.882; p = 0.012) and consuming hay in the diet (OR = 0.323; 95% CI = 0.220–0.473; p < 0.001) were protective factors. In conclusion, ADD has a high prevalence and is usually underdiagnosed, highlighting the need for an exhaustive evaluation of patients during the clinical examination. This study improves our knowledge of ADD and its prevention.
... Bivalent group 2 was given gB1 + gB3 mRNA-LNPs, and pentavalent group 3 was vaccinated with gB1 + gB2 + gB3 + gB4 + gB5 mRNA-LNPs. New Zealand White rabbits were applied in this study due to their intermediate size and a longer life span, which allowed for large collection of blood samples and tissue biopsies from a single animal, investigation of the durability of vaccines 40 , and has been validated to recapitulate Fcmediated effector antibody responses mediated in primates 41 . We evaluated whether bivalent and pentavalent vaccines including multiple gB genotypes could elicit broader protection against multi-genotypic HCMV infections than the monovalent HCMV gB immunogen. ...
Human cytomegalovirus (HCMV) remains the most common congenital infection and infectious complication in immunocompromised patients. The most successful HCMV vaccine to-date, an HCMV glycoprotein B (gB) subunit vaccine adjuvanted with MF59, achieved 50% efficacy against primary HCMV infection. A previous study demonstrated that gB/MF59 vaccinees were less frequently infected with HCMV gB genotype strains most similar to the vaccine strain than strains encoding genetically distinct gB genotypes, suggesting strain-specific immunity accounted for the limited efficacy. To determine whether vaccination with multiple HCMV gB genotypes could increase the breadth of anti-HCMV gB humoral and cellular responses, we immunized 18 female rabbits with monovalent (gB-1), bivalent (gB-1+gB-3), or pentavalent (gB-1+gB-2+gB-3+gB-4+gB-5) gB lipid nanoparticle-encapsulated nucleoside-modified RNA (mRNA-LNP) vaccines. The multivalent vaccine groups did not demonstrate higher magnitude or breadth of the IgG response to the gB ectodomain or cell-associated gB compared to that of monovalent vaccine. Also, the multivalent vaccines did not show an increase in the breadth of neutralization activity and antibody-dependent cellular phagocytosis against HCMV strains encoding distinct gB genotypes. Yet, peripheral blood mononuclear cell-derived T cell responses elicited by multivalent vaccines were of a higher magnitude compared to that of monovalent vaccinated animals against a vaccine-mismatched gB genotype at peak immunogenicity. Our data suggests that inclusion of multivalent gB antigens is beneficial to increase the magnitude of T cell response but not an effective strategy to increase the breadth of anti-HCMV gB antibody responses. Further studies are required to validate whether the multivalent gB mRNA vaccines could effectively increase the T cell response breadth.
... The rabbits were acquired as two age groups: the young group comprised 6.5-month-old rabbits (n = 11), and the older group comprised rabbits between 3.2 and 3.7 years of age (average = 3.3 years old) (n = 11). The 6.5-monthold rabbits are sexually mature young adult rabbits, and the ~ 3.5-year-old rabbits are retired breeders and represent older adults [94]. Male rabbits were used to avoid the effects of female sex hormones on body fluid regulation that occur in hormonally-cycling humans and rodents [95][96][97]. ...
Background
Older adults are more prone to develop systemic dehydration. Systemic dehydration has implications for vocal fold biology by affecting gene and protein expression. The objective of this study was to quantify vocal fold protein changes between two age groups and hydration status, and to investigate the interaction of age and hydration status on protein expression, which has not been investigated in the context of vocal folds before. Comparative proteomics was used to analyze the vocal fold proteome of 6.5-month-old and > 3-year-old rabbits subjected to water ad libitum or water volume restriction protocol.
Results
Young and older adult rabbits ( n = 22) were either euhydrated (water ad libitum) or dehydrated by water volume restriction. Dehydration was confirmed by body weight loss of − 5.4% and − 4.6% in young and older groups, respectively, and a 1.7-fold increase of kidney renin gene expression in the young rabbits. LC-MS/MS identified 2286 proteins in the rabbit vocal folds of young and older adult rabbits combined. Of these, 177, 169, and 81 proteins were significantly ( p ≤ 0.05) affected by age, hydration status, or the interaction of both factors, respectively. Analysis of the interaction effect revealed 32 proteins with opposite change patterns after dehydration between older and young rabbit vocal folds, while 31 proteins were differentially regulated only in the older adult rabbits and ten only in the young rabbits in response to systemic dehydration. The magnitude of changes for either up or downregulated proteins was higher in the older rabbits. These proteins are predominantly related to structural components of the extracellular matrix and muscle layer, suggesting a disturbance in the viscoelastic properties of aging vocal fold tissue, especially when subjected to systemic dehydration.
Conclusions
Water restriction is a laboratory protocol to assess systemic dehydration-related changes in the vocal fold tissue that is translatable to human subjects. Our findings showed a higher number of proteins differentially regulated with a greater magnitude of change in the vocal folds of older adult rabbits in the presence of systemic dehydration compared to younger rabbits. The association of these proteins with vocal fold structure and biomechanical properties suggests that older human subjects may be more vulnerable to the effects of systemic dehydration on vocal function. The clinical implications of these protein changes warrant more investigation, but age should be taken into consideration when evaluating vocal treatment recommendations that interfere with body fluid balance.
... No studies have focused on elderly individuals.The translatability of animal age to human age is usually a key and difficult issue. There are notorious differences between animal species in the span of the neonatal period, juvenile stage, adult stage, and senescence(Andersson et al., 1999;Morford et al. 2011;Andreollo et al. 2012;Geifman and Rubin 2013;Sengupta 2013;Dutta and Sengupta 2016;Agoston 2017;Dutta and Sengupta 2018;Tohyama and Kobayashi 2019;Sengupta and Dutta 2020;Graves et al. 2020). Further information is provided in SupplementalTable 1andFigure 3. ...
Aluminum (Al) salts are commonly used as adjuvants in human and veterinary vaccines for almost a century. Despite this long history of use and the very large number of exposed individuals, data in the literature concerning the fate of these molecules after injection and their potential effects on the nervous system is limited. In the context of (i) an increase of exposure to Al salts through vaccination; (ii) the absence of safety values determined by health regulators; (iii) the lack of robustness of the studies used as references to officially claim Al adjuvant innocuity; (iv) the publication of several animal studies investigating Al salts clearance/biopersistence and neurotoxicity; we have examined in this review all published studies performed on animals and assessing Al adjuvants kinetics, biodistribution, and neuro-modulation since the first work of A. Glenny in the 1920s. The diversity of methodological approaches, results, and potential weaknesses of the 31 collected studies are exposed. A large range of protocols has been used, including a variety of exposure schedule and analyses methods, making comparisons between studies uneasy. Nevertheless, published data highlight that when biopersistence, translocation, or neuromodulation were assessed, they were documented whatever the different in vivo models and methods used. Moreover, the studies pointed out the crucial importance of the different Al adjuvant physicochemical properties and host genetic background on their kinetics, biodistribution, and neuro-modulatory effects. Regarding the state of the art on this key public health topic, further studies are clearly needed to determine the exact safety level of Al salts.
