Wound Healing Delay in the ZDSD Rat

Abstract

Abstract. Animal It is estimated that there are more than 400 million or more people in the world suffering from diabetes mellitus (1). Many diabetic patients have difficulty in healing wounds and the annual cost to manage these wounds exceeds 20 billion dollars (2). In particular, wounds affecting the feet are common, with amputation being a frequent outcome (3). Because of the importance of impaired wound healing in diabetics, animal models of diabetic wound healing are of great interest.Rodent models of diabetic wound healing have received a great deal of focus due to ease of maintenance, cost and availability of genetically modified lines. The full-thickness excisional wound model is a standard approach in which a punch biopsy is used to remove both epidermal and dermal tissues, allowing evaluation of epithelialization, granulation, and angiogenesis, all key processes during physiological wound healing (4). Although wound healing in rodents occurs mainly by contraction, several diabetic rodent models have been used to characterize wound healing in type 2 diabetes, including the db/db mouse, the JCR:LA-cp rat and the Zucker diabetic fatty (ZDF) rat (5-8).The Zucker diabetic Sprague dawley (ZDSD) rat is an animal model of type 2 diabetes and dietary obesity which develop subsequently to chronic dietary manipulation (9, 10). ZDSD rats were developed by cross-breeding diet-induced obesity (DIO) rats derived from Sprague Dawley rats Crl:CD(SD) with ZDF +/+ lean rats. Lacking leptin receptor defects, the ZDSD rat possesses an obese phenotype and the potential to develop overt hyperglycemia between 15 and 21 weeks of age. These characteristics make the ZDSD rat an excellent model of human adult-onset diabetes which develops over time in response to chronic overeating and lack of physical activity. The studies described here were undertaken to determine if the ZDSD rat demonstrates impaired wound healing and might, therefore, be useful as an animal model of delayed healing in type-2 diabetic patients. Materials and MethodsAnimals. Four month old male rats documented to be free of common infectious pathogens were used. All studies were approved by the Institutional Animal Care and Use Committee. Rats were maintained in solid-bottom polycarbonate cages containing abundant hardwood chip bedding. ZDSD rats were obtained from PreClinOmics, Inc., (now a Crown Bioscience company; Indianapolis, IN, USA) and Hsd:Sprague Dawley ® SD ® rats were 55

Zucker Diabetic‐Sprague Dawley (ZDSD) rat: Type 2 diabetes translational research model

“…Most studies reported that ZDSD rats developed obesity with diabetes, whereas one study using HFD reported that both diabetic and non‐diabetic ZDSD rats were larger than SD rats at 17 weeks. The researchers interpreted these observations as evidence that the obesity and diabetes are independent events (Suckow et al., 2017). Adipose tissue generates leptin, a hormone that regulates body weight through food intake and adipose tissue mass (Friedman & Halaas, 1998).…”

“…Common morbidities, such as cardiomyopathy, that are associated with higher risk occurrence in prediabetic persons, have also been reported in the ZDSD rat (Sun et al., 2018). Clinical deteriorations associated with human T2D and observed in the ZDSD rat include delayed wound healing, nephropathy and neuropathy (Davidson et al., 2014; Peterson et al., 2015; Suckow et al., 2017). The recent availability of the ZDSD rat and its potential to model human T2D accurately opens new research avenues to advance basic scientific understanding of diabetes and the translation of results from ‘bench to bedside’.…”

Noncentrifuged Autologous Fat Graft Use On The Treatment Of Lower Extremity Wounds

“…The prevalence of peripheral vascular disease in diabetic patients is 15-30% (7,8). Diabetes and other chronic conditions negatively affect all wound healing processes and the duration and degree of hyperglycemia play a major role in terms of complications (9,10). The deterioration of the metabolic system leads to reduced resistance to infections, which often result in amputation.…”

Next Generation of Spontaneously Diabetic Model of ZDSD Rats with Intact Leptin Signaling Develop Cardiac Dysfunction and Compromised Cardiac Reserve

“…Serum insulin levels displayed bi-phasic fluctuation where pre-diabetic insulin hyper-secretion was noticed between 13-18 weeks, after which insulin levels start to decline [28]. More importantly, the animals showed multiple diabetic late complications such as diabetic nephropathy [29], neuropathy [30] and delayed wound healing [31], which make ZDSD rat an ideal pre-clinical model for study diabetes and related complications. The main aim of this study is to evaluate the cardiac morphology and function in ZDSD rats during the development of diabetes using non-invasive echocardiography and to assess the possibility of using ZDSD rats as a model for the development of therapeutic approaches for treating diabetic cardiomyopathy.…”