EXPERIMENTAL ROTAVIRUS INFECTION IN NEONATAL RATS

Abstract

Although rotavirus (RV) is the commonest cause of acute diarrhoea in children, its pathogenesis remains uncertain. We, therefore, have studied the clinical course and the small intestinal morphometry and pathophysiology of neonatal rats with experimental RV infection. Eight day old rats (n=6 minimum per group) inoculated orally with rat RV, were studied at 12-96 hours post inoculation (HPI) for perfusion, or 12-168 HPI for morphometry at 6 hour intervals up to 24 HPI, and then at 24 hour intervals. Clinical diarrhoea occurred at 24 HPI, which continued for 4-5 days. RV was excreted in stool from 24-72 HPI. Body weight was significantly less than controls (p<0.01) from 24-96 HPI, but no difference was seen at 168 HPI. Small intestinal morphometry showed significant villous destruction, i.e. a reduction in villous height, by 12 HPI (p<0.04) and increased crypt depth (CD) by 48 HPI (p<0.01) in ileum, which continued up to the end of study period (168 HPI). In jejunum, significant villous atrophy was first noted at 18 HPI (p<0.01) and increased CD at 72 HPI (p<0.01), which continued until 72 and 168 HPI respectively. Steady state perfusion in situ of the whole small intestine with plasma electrolyte solution with no glucose showed reduced absorption of water than controls at 12, 72 and 96 HPI (p<0.01), and net secretion at 18, 24 and 48 HPI. This rat model shows that villous destruction by RV is associated with transport defects and both occur before clinical diarrhoea. Crypt hyperplasia occurs afterwards and persists.