Bile duct ligation in neonatal rats: Is it a valid experimental model for biliary atresia studies?

Abstract

BA is the most important disease requiring liver transplantation in children. Common BDL in rats is a classic experimental model to study biliary obstruction. The response of the neonatal animal to BDL has yet to be completely understood and few reports have focused on the behavioral differences of the liver between neonatal and adult animals. Ninety newborn Wistar rats aged six days, weighing 8.0-13.9 g, and 90 adult Wistar rats weighing 199.7-357.0 g, were submitted to BDL. After surgery, they were randomly divided and killed on the 3rd, 5th, 7th, 14th, 21st and 28th day post-BDL. Hepatic biopsies were obtained and the following were measured: (i) semiquantification of the bile ductule proliferation and inflammatory infiltrate by HE stain, (ii) quantification of portal and periportal fibrosis with the Sirius-red stain. Although the initial response of ductule proliferation and inflammatory infiltrate were less intense in the newborn animal, the portal and periportal fibrosis were higher when compared with adult animals (p < 0.0491). These findings may contribute to the understanding of the pathophysiology of BA.

Effects of selective bile duct ligation on liver parenchyma in young animals: histologic and molecular evaluations

“…These findings are similar to those observed in the model of common bile duct ligation [8] and may be explained by bile duct collateral neoformation in the hilum area and by collagen deposition and expansion of the portal area (which increases the denominator of the duct density ratio). The subsequent increase in biliary duct density after the fourth week suggests the maintenance of any stimulus to biliary proliferation.…”

“…In previous experiments using rats subjected to BDL, significant differences were observed between the responses of animals of different ages regarding the ductule proliferation [8]. In addition, the increase in desmin expression was more intense and precocious in newborn than in adult rats [17].…”

“…Although much is known about cell injury and fibrosis induction because of liver diseases, some aspects remain unclear, such as the nature of the differences between the diseases seen in newborn infants and those in older children and adults [8]. The classic experimental model used to study of BO is the common bile duct ligation in rats [5,9,10].…”

Analysis of the reversibility of biliary cirrhosis in young rats submitted to biliary obstruction followed by desobstruction

“…Nowadays, patients with biliary obstruction are submitted to Kasai portoenterostomy as an attempt to restore bile flow 2 and the most important prognostic factor is the age at which portoenterostomy is performed 3,4 . Children untreated before reaching two years of life, die by complications of portal hypertension and liver failure 5 , but good results may be achieved when the child undergoes the surgery before there is a severe loss of liver function 3,4 . On the other hand, even among patients who undergo surgery, some may develop progressive liver fibrosis culminating in cirrhosis.…”

“…On the other hand, even among patients who undergo surgery, some may develop progressive liver fibrosis culminating in cirrhosis. The evolution to transplant necessity is quite frequently, so that biliary atresia is responsible for over 60% of pediatric liver transplants 5 .…”