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Review
. 2020 May;53(5):596-604.
doi: 10.1097/SHK.0000000000001507.

Exploring Clinically-Relevant Experimental Models of Neonatal Shock and Necrotizing Enterocolitis

Affiliations
Review

Exploring Clinically-Relevant Experimental Models of Neonatal Shock and Necrotizing Enterocolitis

Lila S Nolan et al. Shock. 2020 May.

Abstract

Neonatal shock and necrotizing enterocolitis (NEC) are leading causes of morbidity and mortality in premature infants. NEC is a life-threatening gastrointestinal illness, the precise etiology of which is not well understood, but is characterized by an immaturity of the intestinal barrier, altered function of the adaptive immune system, and intestinal dysbiosis. The complexities of NEC and shock in the neonatal population necessitate relevant clinical modeling using newborn animals that mimic the disease in human neonates to better elucidate the pathogenesis and provide an opportunity for the discovery of potential therapeutics. A wide variety of animal species-including rats, mice, piglets, and primates-have been used in developing experimental models of neonatal diseases such as NEC and shock. This review aims to highlight the immunologic differences in neonates compared with adults and provide an assessment of the advantages and drawbacks of established animal models of both NEC and shock using enteral or intraperitoneal induction of bacterial pathogens. The selection of a model has benefits unique to each type of animal species and provides individual opportunities for the development of targeted therapies. This review discusses the clinical and physiologic relevance of animal models and the insight they contribute to the complexities of the specific neonatal diseases: NEC and shock.

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Figures

Figure 1.
Figure 1.. Characteristics of Neonatal Innate and Adaptive Immune Responses.
Newborn infants have distinctive features of the innate and adaptive immune responses when compared with adults. These characteristics result in immune deficits in the infant, particularly in those born preterm. Figure created with Biorender.com.
Figure 2.
Figure 2.
Demonstration of a simple needle-based intraperitoneal injection of a bacterial slurry to induce sepsis in a neonatal mouse.

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