Developmental Susceptibility to Intestinal Injury by Platelet-Activating Factor in the Newborn Rat

Abstract

Platelet-activating factor (PAF) is an important endogenous mediator of neonatal necrotizing enterocolitis (NEC). Injection of PAF into weanling and adult rats causes ischemic bowel necrosis that is morphologically similar to NEC. The purpose of this study was to adapt the PAF model of intestinal injury to the suckling rat and to attempt to alter susceptibility to PAF-induced bowel necrosis by early weaning and formula feeds. At ages 15 to 20 days, rat pups were selected to be weaned to either formula or 5% dextrose or to nurse ad lib (total n = 54). At ages 16, 18, 20, 21, 23, or 25 days of life, animals received PAF (50 μg/kg) and endotoxin (I mg/kg) by intraperitoneal injection. Animals were sacrificed 2 h after injection. Intestinal samples were submitted to be graded by a pathologist in a blinded fashion. Injury scores ranged from 0 to 10, based on the percentage ofvillous necrosis. Prior to age 20 days, minimal histologic injury was present (mean scores on days 16. 18 = 1.7 ± 0.9, 1.7 ± 0.6). Combined injury scores for weaned and nursed animals on days 20 and 23 were significantly greater than on days 16 and 18 (p =. 0001). Histologic injury in the dextrose group was significantly less than the formula-fed group on day 21 and greater on day 25. Suckling rats showed resistance to PAF-induced bowel necrosis prior to 20 days of age, during the middle of the weaning period. Early weaning to formula did not alter susceptibility to injury, which suggests that PAF-acetylhydrolase from breast milk does not confer this resistance to PAF.

Key Words:

• growth and development
• necrotizing enterocolitis
• platelet-activating factor