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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Lipopolysaccharide administration enhances hypoxic-ischemic brain damage in newborn rats
Li Yang1, Hiroshi Sameshima, Tomoaki Ikeda
1Department of Obstetrics and Gynecology, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan.
Insights
Inflammation from lipopolysaccharide (LPS) worsens brain damage caused by hypoxic-ischemic (HI) insult in newborn rats. This effect increases with higher LPS doses, indicating LPS potentiates HI-induced brain injury.
Area of Science:
- Neuroscience
- Perinatal Medicine
- Toxicology
Background:
- Hypoxic-ischemic (HI) insult is a major cause of brain damage in newborns.
- Inflammation is suspected to exacerbate HI-induced brain injury.
- Lipopolysaccharide (LPS) is a potent inflammatory agent.
Purpose of the Study:
- To investigate the combined effect of inflammation and HI insult on perinatal brain damage.
- To examine the dose-response relationship of LPS administration on HI insult in neonatal rats.
Main Methods:
- Neonatal Wistar rats received pre-injections of LPS (0.1, 0.5, or 1 mg/kg) or saline.
- Rats underwent unilateral carotid artery ligation followed by hypoxia.
- Neuronal damage was assessed histologically seven days post-insult.
Main Results:
- Mortality significantly increased in the highest LPS dose group (1 mg/kg LPS/HI).
- No neuronal damage occurred in rats receiving LPS alone.
- LPS significantly increased neuronal loss in the cerebral cortex and hippocampus in a dose-dependent manner when combined with HI.
Conclusions:
- Lipopolysaccharide (LPS) potentiates hypoxic-ischemic (HI) insult.
- The potentiation of HI insult by LPS is dose-dependent.
- Inflammation exacerbates HI-induced brain damage in neonatal rats.
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.
