Aim: To determine whether inflammation and hypoxic-ischemic insult (HI) act additively to cause brain damage in perinatal animals by examining the dose-response effect of lipopolysaccharide (LPS) administration on HI insult in neonatal rat pups.
Methods: Seven-day-old Wistar rats (n = 119) were divided into three groups: (i) a group that received a pre-injection of LPS and HI (LPS/HI, 1 mg/kg, n = 31; 0.5 mg/kg, n = 20; 0.1 mg/kg, n = 17); (ii) a group that received a pre-injection of saline and HI (saline/HI, n = 35); and (iii) those that received LPS alone (1 mg/kg, n = 16). At 4 h after the injection, rat pups from groups (i) and (11) were exposed to unilateral carotid artery ligation, followed by 1 h of hypoxia (8% oxygen in 92% nitrogen) at 33 degrees C. Seven days after the insult, they were sacrificed and their brains removed for histological study. Neuronal damage was categorized as mild, < or =25%; moderate, 25-50%; and severe, > or =50% of surface area on a single section.
Results: Mortality rate during the experiment was significantly increased in the 1 mg/kg of LPS/HI group (12 of 31, 39%) compared with the saline/HI group (0%). No neuronal damage was observed in the LPS only group. However, when LPS was added to HI, neuronal loss in the cerebral cortex and hippocampus was significantly increased in a dose-response manner.
Conclusion: LPS potentiates hypoxic-ischemic insult in a dose-dependent fashion to cause brain damage in neonatal rats.