Effects of tail nerve electrical stimulation on the activation and plasticity of the lumbar locomotor circuits and the prevention of skeletal muscle atrophy after spinal cord transection in rats.

INTRODUCTION: Severe spinal cord injury results in the loss of neurons in the relatively intact spinal cord below the injury area and skeletal muscle atrophy in the paralyzed limbs. These pathological processes are significant obstacles for motor function reconstruction. OBJECTIVE: We performed tail nerve electrical stimulation (TNES) to activate the motor neural circuits below the injury site of the spinal cord to elucidate the regulatory mechanisms of the excitatory afferent neurons in promoting the reconstruction of locomotor function. METHODS: Eight days after T10 spinal cord transection in rats, TNES was performed for 7 weeks. Behavioral scores were assessed weekly. Electrophysiological tests and double retrograde tracings were performed at week 8. RESULTS: After 7 weeks of TNES treatment, there was restoration in innervation, the number of stem cells, and mitochondrial metabolism in the rats' hindlimb muscles. Double retrograde tracings of the tail nerve and sciatic nerve further confirmed the presence of synaptic connections between the tail nerve and central pattern generator (CPG) neurons in the lumbar spinal cord, as well as motor neurons innervating the hindlimb muscles. CONCLUSION: The mechanisms of TNES induced by the stimulation of primary afferent nerve fibers involves efficient activation of the motor neural circuits in the lumbosacral segment, alterations of synaptic plasticity, and the improvement of muscle and nerve regeneration, which provides the structural and functional foundation for the future use of cutting-edge biological treatment strategies to restore voluntary movement of paralyzed hindlimbs.

Comparison between local abdominal and transcutaneous tail vein photobiomodulation in experimental rat model of ulcerative colitis.

Ulcerative colitis (UC) is a chronic autoimmune disease that impacts the quality of life, but current pharmacological treatments are limited. Photobiomodulation (PBM) is a light-based treatment that can be applied either locally or systemically. Here, we compare the effects of local and vascular PBM (VPBM) in an experimental rat model of UC. Male Wistar rats were induced with UC by rectal instillation of acetic acid and treated with either local abdominal PBM or VPBM to the tail vein using a 660-nm LED. The findings indicated that local PBM but not VPBM reduced intestinal histological scores. Both local and VPBM increased mucus production, decreased mast cell degranulation, and modulated TNF-α and IL-1 ß levels in the intestines. Local PBM also affected the expression of the mRNAs for IL-6, TNF-α, and IFN-γ. In conclusion, we suggest that local PBM appears to be more promising than VPBM for treating UC. However, further research is needed to fully understand the mechanisms and to optimize the parameters of PBM for UC treatment.

Pigs' capacity to experience feelings and to suffer from tail lesion, ear lesion and lameness: Exploring citizens and pig farm and abattoir workers' knowledge and perceptions.

The aim of this study was to gain insight into the perceptions of pig farm and abattoir workers as well as lay citizens regarding (1) sentience and (2) positive (intelligent and friendly) and negative (gluttonous, stubborn and dirty) attributes of pigs. We also aimed to investigate the (3) knowledge and perceptions of pig farm and abattoir workers on tail lesion, ear lesion and lameness in pigs and (4) the opinion of lay citizens regarding the likelihood of tail lesions, ear lesions, and lameness causing suffering in pigs and affecting meat quality. Chilean pig farm workers (n = 116), pig abattoir workers (n = 95), and lay citizens (n = 708) were invited on farm, at the abattoir and in public places, respectively, to participate in a survey. Answers were indicated using a 5-point Likert scale (0 = totally disagree; 4 = totally agree). Data were analysed using generalized linear models, including recruitment place and socio-demographic data as predictor variables. Female and lay citizens attributed pigs a higher capacity to experience feelings than male participants and pig farm and abattoir workers (p < 0.05). Lay citizens and workers recruited on farm described pigs as being more intelligent and friendly than those workers recruited at the abattoir (p < 0.001); recruitment place and sex were not associated with participants' perception regarding negative attributes of pigs (p > 0.05). Most lay citizens considered that tail lesions, ear lesions and lameness are likely to cause suffering in pigs and older participants had higher odds of agreeing that tail and ear lesions are likely to affect meat quality (p < 0.05). Finally, the risk factors for tail lesion, ear lesions and lameness pointed out by pig farm and abattoir workers is in line with what has been suggested by experts. Our findings contribute to understand the perception and values of all stakeholders regarding animal welfare, as it is crucial to improve the sustainability of animal production systems.

Epidemiological study of congenital malformations of the vertebral column in French bulldogs, English bulldogs and pugs.

BACKGROUND: Congenital vertebral body malformations (CVBMs) have retrospectively been investigated in British and American canine populations. This study prospectively evaluates occurrence, localization, type and characteristic of CVBM along the entire vertebral column in a cohort of French Bulldogs, English Bulldogs and Pug dogs from Germany. METHODS: Prospective clinical and radiological screenings for CVBM were performed in brachycephalic dogs presented for reasons unrelated to neurological problems. Neurological and orthopaedic examinations as well as radiographs in two orthogonal planes of the entire vertebral column including the tail were performed in all dogs. Cobb angle and vertebral step were determined. Associations between CVBM, tail malformation, neurological deficits and occurrence of concurrent orthopaedic diseases were investigated. RESULTS: A total of 707 VBMs were identified in the whole vertebral column of 169 of 265 brachycephalic dogs. The most common types of CVBMs were ventral wedge shape (48%), dorsal wedge shape (14%) and shortened vertebral body (14%). A new type of malformation was investigated: dorsal wedge shape vertebrae. There was significant association between severe tail malformations with CVBM. Neurological deficits were significantly associated with ventrolateral wedge shape, dorso lateral hemivertebrae, Cobb angle > 30% and vertebral step ≥1.75 mm. Orthopaedic conditions were not significantly associated with CVBM. CONCLUSION: Kyphotic Cobb angle and vertebral step are radiological findings associated with neurological deficits. We propose severe tail malformation as an easy and accurate selection factor for determining breeding dogs.

An efficient, non-invasive approach for in-vivo sampling of hair follicles: design and applications in monitoring DNA damage and aging.

In accordance with the 3 Rs principle (to replace, reduce and refine) animal models in biomedical research, we have developed and applied a new approach for sampling and analyzing hair follicles in various experimental settings. This involves use of a convenient device for non-invasive collection of hair follicles and processing methods that provide sufficient amounts of biological material to replace stressful and painful biopsies. Moreover, the main components of hair follicles are live cells of epithelial origin, which are highly relevant for most types of malignant tumors, so they provide opportunities for studying aging-related pathologies including cancer. Here, we report the successful use of the method to obtain mouse hair follicular cells for genotyping, quantitative PCR, and quantitative immunofluorescence. We present proof of concept data demonstrating its utility for routine genotyping and monitoring changes in quality and expression levels of selected proteins in mice after gamma irradiation and during natural or experimentally induced aging. We also performed pilot translation of animal experiments to human hair follicles irradiated ex vivo. Our results highlight the value of hair follicles as biological material for convenient in vivo sampling and processing in both translational research and routine applications, with a broad range of ethical and logistic advantages over currently used biopsy-based approaches.

Effect of a dietary supplement on the reduction of lymphedema-progression in mouse tail-cut model.

OBJECTIVE: The aim of our study was to evaluate in vivo, in a mouse tail model of lymphedema, the effects of a dietary supplement, Garlive®, based on hydroxytyrosol from olive leaves, spermidine from rice seeds, hesperidin from citrus fruits and vitamin A. Hydroxytyrosol has anti-inflammatory, antioxidant and antimicrobial activities and inhibits leukotriene B4 generation; spermidine is able to inhibit the production of pro-inflammatory cytokines and mediators; hesperidin inhibits the secretion of pro-inflammatory cytokines: IFN-γ, IL-2, IL-4, IL-10; vitamin A deficiency was shown to induce inflammation and aggravate existing inflammatory states, whereas supplementation with vitamin A could ameliorate inflammation. MATERIALS AND METHODS: The active compounds were included in tablets: 250 mg of olive leaf extract titrated in 10% hydroxytyrosol, 200 mg of citrus fruits extract titrated in 60% hesperidin, 10 mg of rice (Oryza sativa) seeds extract titrated in 1% spermidine and 0.8 mg of vitamin A. Mice of an inbred group were randomly selected and divided in the control group and drug-treated group. The wound necessary for lymphedema generation was made on the tail of each mice 1 cm below the base of the trunk. RESULTS: After surgical intervention, there was a gradual increase in the circumference of both ends of the wound. The control group showed higher increase of tail volume than the drug-treated group. The differences in tail swelling between the control group and the drug-treated group were significantly different. The peak of swelling was anticipated to the 6th day in the drug-treated group, whereas in the control group the peak was reached later on. CONCLUSIONS: The tested drug prevented the induction of swelling from day 5th of wound creation and decreased the duration of swelling, favoring the wound healing.

Effects of physical impairments on fitness correlates of the white-footed mouse, Peromyscus leucopus.

Physical impairments are widely assumed to reduce the viability of individual animals, but their impacts on individuals within natural populations of vertebrates are rarely quantified. By monitoring wild populations of white-footed mice over 26 years, we assessed whether missing or deformed limbs, tail or eyes influenced the survival, body mass, movement and ectoparasite burden of their bearers. Of the 27 244 individuals monitored, 543 (2%) had visible physical impairments. Persistence times (survival) were similar between mice with and without impairments. Mice with eye and tail impairments had 5% and 6% greater mass, respectively, than unimpaired mice. Mice with tail impairments had larger home ranges than did unimpaired mice. Burdens of black-legged ticks (Ixodes scapularis) were higher among mice with tail and limb impairments while burdens of bot fly larvae (Cuterebra) were higher among mice with cataracts compared to mice without impairments. Our findings do not support the presupposition that physical impairments reduce viability in their bearers and are inconsistent with the devaluation of impaired individuals that pervaded early thinking in evolutionary biology.

Etiological characteristics of "tail blister disease" of Australian redclaw crayfish (Cherax quadricarinatus).

In November 2019, an acute disease outbreak in Australian redclaw crayfish (Cherax quadricarinatus) occurred in a farm in Hubei, China, with a cumulative mortality rate of over 80%. One of the characteristic symptoms of the disease was blisters on the tail. This symptom is also common in diseased Procambarus clarkii every year in this country, but the causative agent has not been determined. This study analyzed the etiological characteristics of this disease. Bacterial isolation and identification combined with high-throughput sequencing analysis were conducted to obtain the microbiota characteristics in the hemolymph, hepatopancreas, and intestines. Results showed that this outbreak was caused by infection from Aeromonas hydrophila and Aeromonas veronii. The underlying cause was stress imposed on crayfish during transferring from outdoor pond to indoor pond because of temperature drops. Aeromonas infection caused remarkable changes in the structure of the microbial composition in the hemolymph, hepatopancreas, and intestines of the crayfish. The abundance of Aeromonas in the hemolymph of the sick crayfish was as high as 99.33%. In particular, KEGG metabolic pathway analysis showed that some antibiotic synthesis, enterobactin biosynthesis, and myo-inositol degradation pathways were abundant in healthy crayfish hemolymphs, which may be the mechanism of maintaining crayfish health. Conversely, inhibition of these pathways led to the disorder of microbiota structure, finally leading to the occurrence of diseases. To the knowledge of the authors, this study was the first to use high-throughput amplicon sequencing targeting the 16S rRNA gene to find the causative bacteria in aquatic animals. This protocol can provide more comprehensive and reliable evidence for pathogen identification, even if the pathogenic bacteria are anaerobes or other hard-to-culture bacteria.

A Murine Tail Lymphedema Model.

Lymphedema is extremity swelling caused by lymphatic dysfunction. The affected limb enlarges because of accumulation of fluid, adipose, and fibrosis. There is no cure for this disease. A mouse tail model that uses a focal full thickness skin excision near the base of the tail, resulting in tail swelling, has been used to study lymphedema. However, this model may result in vascular comprise and consequent tail necrosis and early tail swelling resolution, limiting its clinical translatability. The chronic murine tail lymphedema model induces sustained lymphedema over 15 weeks and a reliable perfusion to the tail. Enhancements of the traditional murine tail lymphedema model include 1) precise full thickness excision and lymphatic clipping using a surgical microscope, 2) confirmation of post-operative arterial and venous perfusion using high resolution laser speckle, and 3) functional assessment using indocyanine green near infrared laser lymphangiography. We also use tissue nanotransfection technology (TNT) for novel non-viral, transcutaneous, focal delivery of genetic cargo to the mouse tail vasculature.

A Simple and Quick Method for Decalcification Using Mouse Tail as a Model for Preparation of Lymphedema Study.

The disadvantage of 10% EDTA decalcification is a long time-consuming. It needs to identify a quick and straightforward decalcification method when the preparation of lymphedema models using mouse tail which was a sample of bone wrapped in other tissues. In the present study, mouse tail samples were decalcified in 10% EDTA at 25, 37, and 42°C, respectively, with continuous shaking (150 rpm/min). The histologic integrity of samples was evaluated by hematoxylin and eosin staining, and the preservation of antigenicity was tested by either immunohistochemistry or immunofluorescence. The decalcification was distinctly accelerated by temperature. Results of hematoxylin and eosin staining were similar among different temperature groups. Immunohistochemistry and immunofluorescence staining revealed almost no signals in samples decalcified at 42°C for 1 week. Clear signals were detected when samples were decalcified at 37 and 25°C.

A deep learning approach for staging embryonic tissue isolates with small data.

Machine learning approaches are becoming increasingly widespread and are now present in most areas of research. Their recent surge can be explained in part due to our ability to generate and store enormous amounts of data with which to train these models. The requirement for large training sets is also responsible for limiting further potential applications of machine learning, particularly in fields where data tend to be scarce such as developmental biology. However, recent research seems to indicate that machine learning and Big Data can sometimes be decoupled to train models with modest amounts of data. In this work we set out to train a CNN-based classifier to stage zebrafish tail buds at four different stages of development using small information-rich data sets. Our results show that two and three dimensional convolutional neural networks can be trained to stage developing zebrafish tail buds based on both morphological and gene expression confocal microscopy images, achieving in each case up to 100% test accuracy scores. Importantly, we show that high accuracy can be achieved with data set sizes of under 100 images, much smaller than the typical training set size for a convolutional neural net. Furthermore, our classifier shows that it is possible to stage isolated embryonic structures without the need to refer to classic developmental landmarks in the whole embryo, which will be particularly useful to stage 3D culture in vitro systems such as organoids. We hope that this work will provide a proof of principle that will help dispel the myth that large data set sizes are always required to train CNNs, and encourage researchers in fields where data are scarce to also apply ML approaches.

Validation of laser scanning confocal microscopy as a diagnostic method for lymphedema using a rat model.

Most previous diagnostic methods for lymphedema are invasive. Laser scanning confocal microscopy (LSCM) combines laser and computer image processing technology, is capable of increasing the resolution of optical microscopy by 30-40%, and boasts a comparable resolution to that of histological examination. We constructed the rat tail lymphedema model to simulate secondary lymphedema and to validate the noninvasive technique of in vivo reflectance LSCM for the diagnosis of lymphedema. The rat tail lymphedema model was constructed by cutting and ligating the lymphatic vessels in the rat tail. Lymphedema in the postoperative rat tail was assessed by a comprehensive range of methods including the change of rat tail diameter, lymphocytic radionuclide imaging, LSCM, and immunohistochemistry using a specific lymphatic vessel marker, prospero homeobox protein 1 (PROX1). The noninvasive LSCM method along with other techniques validated the rat tail lymphedema model. LSCM was used to perform qualitative and quantitative evaluation of the state and extent of lymphedema in the rat tail model. Receiver operating characteristic (ROC) curve analysis, which provided an area under the curve (AUC) value of 0.861, supported the feasibility of using LSCM as a reliable diagnostic technique for lymphedema. The rat tail lymphedema model can be successfully constructed by cutting and ligating the lymphatic vessels in the rat tail. Although LSCM cannot replace the method of skin biopsy examination, it offers a painless and noninvasive alternative for diagnosing lymphedema. Thus, LSCM can potentially be adopted in clinical practice as a supporting method to be used in combination with other techniques.

A modified mouse-tail lymphedema model.

One of the main obstacles to studying the pathophysiology of lymphedema development is the lack of appropriate experimental models. Fol-lowing up on a mouse-tail method that has been described, we performed changes to the method which made it easier to perform in our hands and demonstrated similar results. Twenty C57Black mice were operated on using the previous tech-nique and euthanized after 3 or 6 weeks. Another twenty mice were submitted to the new technique developed in our laboratory and euthanized at the same time points. Tissue samples were collected from the proximal part of the tail (control) and from the distal part (lymphedema) for both mod-els. Animals in both operative groups developed marked edema in the distal part of the tail. This was characterized by lymph vessels dilation, edema, inflammatory cell infiltration, and adipose tissue deposition. Lymphedema was detected after 3 weeks in both models, reaching its maximum after 6 weeks. Adipocytes detected by histology (Oil red O staining) and molecular markers for adipogenesis, lymphangiogenesis and inflam-mation (lipin 1 and 2, SLP76, and F4-80) were demonstrated to be increased equally in both models. In conclusion, both models provide a reliable method to study lymphedema pathophys-iology. However, our modified technique is easier and faster to perform while still providing reliable and consistent results.

Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.

Wound healing is a complex process that requires the orderly progression of inflammation, granulation tissue formation, fibrosis, and resolution. Murine models provide valuable mechanistic insight into these processes; however, no single model fully addresses all aspects of the wound healing response. Instead, it is ideal to use multiple models to address the different aspects of wound healing. Here, two different methods that address diverse aspects of the wound healing response are described. In the first model, polyvinyl alcohol sponges are subcutaneously implanted along the mouse dorsum. Following sponge retrieval, cells can be isolated by mechanical disruption, and fluids can be extracted by centrifugation, thus allowing for a detailed characterization of cellular and cytokine responses in the acute wound environment. A limitation of this model is the inability to assess the rate of wound closure. For this, a tail skin excision model is utilized. In this model, a 10 mm x 3 mm rectangular piece of tail skin is excised along the dorsal surface, near the base of the tail. This model can be easily photographed for planimetric analysis to determine healing rates and can be excised for histological analysis. Both described methods can be utilized in genetically altered mouse strains, or in conjunction with models of comorbid conditions, such as diabetes, aging, or secondary infection, in order to elucidate wound healing mechanisms.

Influence of Genetic Background and Sex on Gene Expression in the Mouse (Mus musculus) Tail in a Model of Intervertebral Disc Injury.

To facilitate rational experimental design and fulfill the NIH requirement of including sex as a biologic variable, we examined the influences of genetic background and sex on responses to intervertebral disc (IVD) injury in the mouse tail. The goal of this study was to compare gene expression and histologic changes in response to a tail IVD injury (needle puncture) in male and female mice on the DBA and C57BL/6 (B6) backgrounds. We hypothesized that extracellular matrix gene expression in response to IVD injury differs between mice of different genetic backgrounds and sex. Consistent changes were detected in gene expression and histologic features after IVD injury in mice on both genetic backgrounds and sexes. In particular, expression of col1a1 and adam8 was higher in the injured IVD of DBA mice than B6 mice. Conversely, col2a1 expression was higher in B6 mice than DBA mice. Sex-associated differences were significant only in B6 mice, in which col2a1 expression was greater in male mice than in female. Histologic differences in response to injury were not apparent between DBA and B6 mice or between males and females. In conclusion, mouse tail IVD showed sex- and strain-related changes in gene expression and histology after needle puncture. The magnitude of change in gene expression differed with regard to genetic background and, to a lesser degree, sex.

Frequency-dependent changes in mitochondrial number and generation of reactive oxygen species in a rat model of vibration-induced injury.

Regular use of vibrating hand tools results in cold-induced vasoconstriction, finger blanching, and a reduction in tactile sensitivity and manual dexterity. Depending upon the length and frequency, vibration induces regeneration, or dysfunction and apoptosis, inflammation and an increase in reactive oxygen species (ROS) levels. These changes may be associated with mitochondria, this study examined the effects of vibration on total and functional mitochondria number. Male rats were exposed to restraint or tail vibration at 62.5, 125, or 250 Hz. The frequency-dependent effects of vibration on mitochondrial number and generation of oxidative stress were examined. After 10 days of exposure at 125 Hz, ventral tail arteries (VTA) were constricted and there was an increase in mitochondrial number and intensity of ROS staining. In the skin, the influence of vibration on arterioles displayed a similar but insignificant response in VTA. There was also a reduction in the number of small nerves with exposure to vibration at 250 Hz, and a reduction in mitochondrial number in nerves in restrained and all vibrated conditions. There was a significant rise in the size of the sensory receptors with vibration at 125 Hz, and an elevation in ROS levels. Based upon these results, mitochondria number and activity are affected by vibration, especially at frequencies at or near resonance. The influence of vibration on the vascular system may either be adaptive or maladaptive. However, the effects on cutaneous nerves might be a precursor to loss of innervation and sensory function noted in workers exposed to vibration.

Evaluation of an automated assessment system for ear and tail lesions as animal welfare indicators in pigs at slaughter.

The aim of this pilot study was to develop and evaluate an automated system for the assessment of ear and tail lesions as welfare indicators in pigs at the abattoir. A camera-based system was constructed to enable automatic assessment. This was evaluated in comparison to a standard observer, defined as skilled human veterinary observer, based on 5952 carcasses. We detected significant values for ear lesions (sensitivity, 77.0; specificity, 96.5; accuracy, 95.4%) and good values for tail lesions (sensitivity, 77.8%; specificity, 99.7%; accuracy, 99.5%). The reliabilities of assessments by four individual human observers directly at the abattoir and the camera system were calculated using Krippendorff's alpha. These varied between 0.42 and 0.67 for ear lesions and 0.42 and 0.55 for tail lesions, while better values were reached for the agreement between the system and picture-based evaluation (0.64 for ear lesions and 0.75 for tail lesions). More scientific evaluations at different abattoirs are now needed to further test and improve the camera-based system and its various scopes of application.

Ethanol induces skin hyperpigmentation in mice with aldehyde dehydrogenase 2 deficiency.

Alcohol induces various cutaneous changes, such as palmar erythema and jaundice. However, alcohol-induced skin hyperpigmentation due to melanin deposition has not been reported. Aldehyde dehydrogenase 2 (ALDH2), one of 19 human ALDH isozymes, metabolizes endogenous and exogenous aldehydes to their respective carboxylic acids. Reduced ALDH2 greatly affects acetaldehyde metabolism, leading to its accumulation in the body after the consumption of alcohol and the consequent development of a wide range of phenotypes. In the present study, we report a novel phenotype manifesting in a mouse model with the altered expression of ALDH2. Aldh2 knockout (Aldh2+/- and Aldh2-/-) and wild-type (Aldh2+/+) mice were fed a standard solid rodent chow and a bottle of ethanol solution at concentrations of 0%, 3%, 10%, or 20% (v/v) for more than 10 weeks. The intensity of their skin pigmentation was evaluated by macroscopic observation. Ethanol-exposed Aldh2+/- and Aldh2-/- mice exhibited dose-dependent skin pigmentation in areas of hairless skin, including the soles of the paws and tail; no such changes were observed in wild-type mice. The intensity of skin pigmentation correlated with the number of Aldh2 alleles that were altered in the mice (i.e., 0, 1 and 2 for Aldh2+/+, Aldh2+/-, Aldh2-/-, respectively). Interestingly, the skin pigmentation changes reversed upon the discontinuation of ethanol. The histological examination of the pigmented skin demonstrated the presence of melanin-like deposits, mainly in the epidermis. In conclusion, we report a novel finding that the intake of ethanol induces skin hyperpigmentation in an ALDH2 activity-dependent manner.

A Novel Model for Cutaneous Wound Healing and Scarring in the Rat.

BACKGROUND: Current rodent models of wound healing and scarring are flawed because of rapid wound contraction and inconspicuous scarring after healing, which is not closely parallel to the physiologic process in humans. This study aimed to establish a novel model of wound healing and scarring in rats. METHODS: Excisional wounds were generated in rat tail or dorsal skin and histologic changes and wound contraction were assessed 2, 10, and 16 days after injury. After healing, rat tail scar was investigated for 24 consecutive weeks by histologic and immunohistochemical staining. Finally, a stretched scar model was generated in rat tail with high or low strain after reepithelialization to mimic human hypertrophic scars. The tail hypertrophic scars were analyzed by histology, immunohistochemical staining, and mRNA quantification 0, 2, 6, 12, and 24 weeks after stretching. RESULTS: Compared with the dorsal wounds, a larger dermal gap percentage (p < 0.05) and more pronounced granulation were found in rat tail wounds. Tail scars remained conspicuous and underwent maturation over 24 weeks after wound healing. In addition, high mechanical strain induced significantly increased scar area (p < 0.01), scar height (p < 0.05), vessel density (p < 0.01) and hypertrophic scar-related molecule expression, and distorted collagen arrangement in rat tail scars. CONCLUSIONS: The rat tail model exhibits minor wound contraction and biological features analogous to both normotrophic and hypertrophic scar in humans when generated with or without stretching, respectively. It is a promising new model for studies of both cutaneous wound healing and scarring.