A spectrum of intestinal injury models in neonatal mice.

PURPOSE: To compare the degree of necrotizing enterocolitis (NEC)-like damage under different stress conditions in neonatal mice.

METHODS: 5-day-old C57BL/6 mice were assigned to: (A) breastfed and no stress factors; (B) breastfed+maternal separation (3 h daily); (C) breastfed+hypoxia+lipopolysaccharide (LPS-4 mg/kg/day); (D) hyperosmolar formula+hypoxia+LPS. Mice were killed at 9 days of life. Ileum and colon were stained for hematoxylin/eosin and blindly assessed. A scoring ≥2 was considered NEC. Data were compared using one-way ANOVA and reported as median (range).

RESULTS: Ileum-Mucosal injury was mild in group B (0.0-1). Hypoxia+LPS induced greater injury in group C (1.6, 1-2.5; p < 0.0001 to B) and D (2, 0.5-3.5; p < 0.0001 to B). There were no differences between group C and D (p = n.s.). There were no cases of NEC in group A or B, whereas NEC was present in 36 % group C and 68 % group D mice. Colon-a similar degree of mucosal injury was observed among group B (2, 1-3), C (1.7, 0-3) and D (1.5, 1-3; p = n.s.). NEC was present in 75 % of group B, 50 % of group C and 86 % of group D.

CONCLUSION: These models establish a spectrum of intestinal injury and are useful to investigate the variability of neonatal intestinal diseases, such as NEC.