Modeling trauma in rats: similarities to humans and potential pitfalls to consider

Abstract

Trauma is the leading cause of mortality in humans below the age of 40. Patients injured by accidents frequently suffer severe multiple trauma, which is life-threatening and leads to death in many cases. In multiply injured patients, thoracic trauma constitutes the third most common cause of mortality after abdominal injury and head trauma. Furthermore, 40–50% of all trauma-related deaths within the first 48 h after hospital admission result from uncontrolled hemorrhage. Physical trauma and hemorrhage are frequently associated with complex pathophysiological and immunological responses. To develop a greater understanding of the mechanisms of single and/or multiple trauma, reliable and reproducible animal models, fulfilling the ethical 3 R’s criteria (Replacement, Reduction and Refinement), established by Russell and Burch in ‘The Principles of Human Experimental Technique’ (published 1959), are required. These should reflect both the complex pathophysiological and the immunological alterations induced by trauma, with the objective to translate the findings to the human situation, providing new clinical treatment approaches for patients affected by severe trauma. Small animal models are the most frequently used in trauma research. Rattus norvegicus was the first mammalian species domesticated for scientific research, dating back to 1830. To date, there exist numerous well-established procedures to mimic different forms of injury patterns in rats, animals that are uncomplicated in handling and housing. Nevertheless, there are some physiological and genetic differences between humans and rats, which should be carefully considered when rats are chosen as a model organism. The aim of this review is to illustrate the advantages as well as the disadvantages of rat models, which should be considered in trauma research when selecting an appropriate in vivo model. Being the most common and important models in trauma research, this review focuses on hemorrhagic shock, blunt chest trauma, bone fracture, skin and soft-tissue trauma, burns, traumatic brain injury and polytrauma.

Comparative Analysis of the Host Response in a Rat Model of Deep-Partial and Full-Thickness Burn Wounds With Pseudomonas aeruginosa Infection

“…One of the limitations of this model is that only minimal results concerning wound healing can be ascertained since it only extends till the very early stages of healing (if at all). Rats utilize contraction for wound closure, which typically minimizes risks of infection and/or sepsis (Abdullahi et al, 2014;Weber et al, 2019). That said, some re-epithelization and granulation tissue was noted by the pathologist, particularly in the DPT burn wounds (data not shown).…”

“…Models involving larger burns (i.e., greater TBSA) and bacterial infection typically have a shorter time course or result in high mortality of the animals. A lower TBSA, coupled with the rapid diversification between rat and human immune systems, may explain the minimal effects seen in systemic responses (Weber et al, 2019). While we did see cases of sepsis, typically in the FT burns, animals survived the course of the study.…”

Therapeutic Applications of Stem Cells and Extracellular Vesicles in Emergency Care: Futuristic Perspectives

“…Their beneficial effects in trauma can be summarized as migration and integration into the site of injury and respond to immunostimulatory molecules defined as damage-associated molecular patterns. Besides, they generate an anti-inflammatory and pro-regenerative microenvironment through secreting factors that activate the growth and differentiation of adjacent cells, stimulate angiogenic activity, regulate functions of endothelial cells and fibroblasts, and inhibit fibrosis [ 25 ]. A previous systematic review and meta-analysis study investigating the efficacy of MSC transplantation in animal models of TBI suggested that MSCs might have beneficial effects on locomotor recovery [ 26 ].…”

Collective Locomotion of Human Cells, Wound Healing and Their Control by Extracts and Isolated Compounds from Marine Invertebrates

“…However, it is worth-mentioning that, although small animal models are commonly used for wound healing research, they display some biological limitations due to the differences in the histological architecture of rodent vs. human skin, and in the primary physiological act of healing, i.e., myofibroblast contraction for rodents vs. re-epithelization for humans. Other experimental models, such as the porcine one, have been proven to be more linkable with the human healing process, but the costs of housing and the difficulties in handling have limited their usability for first-line exploratory research [23,24]. Another aspect to consider is that "pure" scarring-free regeneration, which only sees new cells completely replacing the lost ones, is very uncommon in humans.…”