Animal models in general remain the mainstay of sepsis and trauma research, and the mouse remains the model of choice for mechanistic and interventional studies. The Animal Studies Core collaborates with investigators in other programs to study the important comorbidities associated with sepsis and critical illness.
Although recent studies have questioned the value of murine models in inflammation research in general, we continue to maintain that well designed interventional animal studies have value in delineating individual immunological components of critical illness. Over the past decade, the Core has successfully developed and validated a murine model of chronic critical illness (CCI) in response to sepsis that recapitulates much of the underlying processes seen in human persistent inflammation, immunosuppression and catabolism syndrome (PICS). The Animal Studies Core provides aged and transgenic animals and models that are an adjunct to the observational clinical studies, and are meant to mechanistically dissect individual contributions to the host response. Therefore, the overall objectives of the core include:
- To establish a central core resource for the conduct of the studies using the murine model of polymicrobial sepsis, produced by cecal ligation and puncture (CLP), as well as severe polytrauma and hemorrhagic shock.
- To maintain breeding colonies and continue refinement of murine models to more closely approximate the human setting of severe sepsis, polytrauma and critical illness, including obesity and metabolic syndrome, chronic renal disease, Alzheimer’s Disease and related dementias, and immune suppression.
By centralizing animal protocols and management into a single Core, the Program achieves: (1) efficiency in resource utilization, (2) assurance of standardized procedures of animal models with reproducible outcomes, (3) centralized animal purchasing and maintenance, and (4) consolidated communication with the IACUC and Institutional Animal Care Services to maintain an appropriate oversight for the humane use of living animals in USDA Category E research. Reproducible, well described and published models of sepsis and chronic critical illness are the requisite tools to complement the clinical investigations.