Necrotizing enterocolitis: clinical concepts and pathogenetic mechanisms

Necrotizing enterocolitis: clinical concepts and pathogenetic mechanisms Necrotizing enterocolitis (NEC) is an acute inflammatory disease that affects the intestine of neonates resulting in intestinal necrosis, systemic sepsis and multi-system organ failure (Lin and Stoll, 2006). It is the leading cause of death and long-term disability from gastrointestinal disease in preterm infants (Blakely et al., 2005). NEC affects approximately 20% of preterm infants and is gradually increasing in frequency, owing in part to the increased number of preterm infants that are born each year (Feng et al., 2005; Henry and Moss, 2005; Hsueh et al., 2003; Stoll, 1994; Warner and Warner, 2005). NEC is not only one of the most serious clinical problems to affect neonates, but also one of the most challenging to treat. Up to one-third of all babies with NEC in North America die. Challenges in the treatment of NEC are compounded by the fact that the mechanisms leading to NEC development are incompletely understood. Whereas treatment of early stage NEC may be managed by a combination of antibiotics and cessation of oral feeds, advanced cases, in which intestinal necrosis is present, require intestinal resection or abdominal drainage and can be a risky undertaking in these sick, fragile patients (Henry and Moss, 2008). Clearly, a more complete understanding of the causes of NEC is required to more effectively design therapeutic strategies. NEC typically develops after the onset of enteral feeds and when the intestinal tract has become colonized; several lines of evidence indicate that the interaction between indigenous bacteria and the newborn intestine have a crucial role in NEC pathogenesis (Anand et al., 2007; Grave et al., 2007). Although a more complete discussion of the current thinking regarding the pathogenesis of NEC is beyond the scope of the current work, several recent reviews have explored the pathogenesis of NEC in detail (Anand et al., 2007; Frost et al., 2008; Lin et al., 2008). A conclusion shared by many investigators in the field is that, despite several decades of work into the pathogenesis of NEC, the overall mortality rate remains high and our overall understanding of its causes remains correspondingly low. As such, the development of reliable and reproducible animal models for the study of NEC remains a crucial component in our attempt to determine its underlying causes. This review seeks to examine the animal models that have been developed in the study of NEC over the past 30 years, and will highlight the various strengths and weaknesses of each experimental approach while discussing potential directions for the development of models for the future.