Role of Asphyxia and Feeding in a Neonatal Rat Model of Necrotizing Enterocolitis

Abstract

Necrotizing enterocolitis (NEC) is a common gastrointestinal disorder affecting premature infants. To investigate critically the importance of the purported risk factors of NEC (formula feeding, asphyxia, bacteria, and prematurity), we developed a neonatal rat model that closely mimics the human disease. Full-term and premature newborn rats were stressed with formula feeding, asphyxia, and/or exogenous bacterial colonization and subsequently evaluated grossly and histologically for the development of intestinal injury. We found that most animals treated with asphyxia, formula feeding, and bacteria developed NEC (77%) and died (86%) by 96 h. All maternally fed animals treated with asphyxia and bacterial colonization survived and had normal intestinal histology. Furthermore, asphyxia was a critical instigating factor, because formula and bacterial exposure without asphyxia resulted in normal intestine and minimal mortality (12%). Enteral bacterial colonization was not a significant determinant of NEC in this model. We conclude that the neonatal rat model is an excellent test system for the study of NEC. As in the human disease, asphyxia and formula feeding play an important role in the pathophysiology of experimental NEC.

The viral dsRNA analogue poly (I:C) induces necrotizing enterocolitis in neonatal mice

“…This increase corresponded to a total of about 1,000 neutrophils distributed over the entire small intestine. In combination with the low transcriptional activity of proinflammatory cytokines measured in this study, this slight increase of neutrophils is well in line with the minimal inflammation seen in experimental murine NEC by other groups (13,29).…”

“…Grade 0: intact epithelium with villus structure; 1: superficial epithelial cell sloughing; 2: mid-villous necrosis; 3: complete villous necrosis; and 4: transmural necrosis. Samples with histological scores of 3 or higher were considered positive for NEC (modified protocol of Caplan et al (29)). The modification was made to ensure positive selection for NEC by excluding unlikely graded artificial lesions, as observed in some breastfed animals, caused by luminal air bubbles during the fixation process which might mimic "grade 2 " lesions (Supplementary Figure S3 online).…”

“…Brain, liver, lung, spleen, and kidney samples were investigated for signs of tissue damage as well. Intestinal tissue injury scores were assigned by two blinded investigators based on the histologic injury scoring system described by Caplan et al (29): NEC scores from 0 to 4 were assigned for each sample. Grade 0: intact epithelium with villus structure; 1: superficial epithelial cell sloughing; 2: mid-villous necrosis; 3: complete villous necrosis; and 4: transmural necrosis.…”

Intestinal Epithelial Cell Apoptosis, Immunoregulatory Molecules, and Necrotizing Enterocolitisb

“…Additional experiments have evaluated the importance of PAF in neonatal rats using the typical risk factors of NEC, including asphyxia and formula feeding [16]. In this model, we have shown that PAF receptor blockade reduces the incidence of NEC, and that the PAF-degrading enzyme PAF-AH given with enteral feeding interferes with the initiation of NEC [17,18].…”

Avaliação de um modelo experimental de enterocolite necrosante neonatal em ratos

“…A combinação de isquemia gastrointestinal, fruto de uma redistribuição do fluxo sangüíneo esplâncnico para órgãos vitais como coração e cérebro, alimentação enteral, possivelmente predispondo à lesão da camada mucosa e mais a translocação de bactérias patogênicas, tudo isto associado a uma imaturidade dos mecanismos imunitários intestinais, estariam envolvidos em seu desenvolvimento 1,2 . Muitos modelos animais foram usados para avaliar os efeitos da hipóxia na etiopatogenia da ECN e demonstraram que o decréscimo da perfusão intestinal e que a lesão tecidual seriam causadas por um mecanismo de isquemia e reperfusão [3][4][5][6][7][8][9][10][11][12] . O objetivo de nosso estudo é avaliar um modelo experimental de ECN em ratos proposto por em 1995 por Okur e col. 9 .…”