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Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Hypercholesterolemic diet applied to rat dams protects their offspring against cognitive deficits. Simulated neonatal
1Department of Animal Physiology, Institute of General and Molecular Biology, Nicholas Copernicus University, ul. Gagarina 9, 87-100 Torun, Poland. iwo.bohr@newcastle.ac.uk
Insights
High dietary cholesterol protected neonatal rats from cognitive deficits caused by anoxia. This suggests cholesterol
Area of Science:
- Neuroscience
- Developmental Biology
- Metabolic Disorders
Background:
- Cholesterol is increasingly recognized for its neuroprotective roles, particularly in conditions like stroke and Alzheimer's disease (AD).
- Neonatal anoxia, a critical event during birth, can lead to significant long-term neurological impairments, including cognitive deficits.
Purpose of the Study:
- To investigate the potential neuroprotective effects of maternal dietary cholesterol on cognitive function in rat pups exposed to simulated neonatal anoxia.
- To explore the relationship between cholesterol levels and anoxia-induced neurodevelopmental deficits.
Main Methods:
- Rat dams were fed either a standard or a cholesterol-enriched diet.
- Offspring were exposed to simulated neonatal anoxia or served as controls.
- Spatial memory was assessed using linear maze and Morris water maze tests at 1.5 months of age.
- Plasma cholesterol levels were measured post-behavioral testing.
Main Results:
- Neonatal anoxia impaired spatial memory in rats from dams on a standard diet.
- Rats exposed to anoxia but whose dams received a cholesterol-enriched diet performed comparably to control animals.
- Anoxic offspring on a standard diet exhibited elevated blood cholesterol levels, suggesting an adaptive response.
Conclusions:
- Maternal dietary cholesterol intake can mitigate cognitive impairments resulting from neonatal anoxia in offspring.
- The anoxia-induced rise in blood cholesterol may represent a physiological adaptive mechanism against neurotoxic processes.
- Findings offer insights into cholesterol's role in neurodevelopmental disorders and potential therapeutic strategies for conditions like AD.
Abstract:
There is accumulating data suggesting a neuroprotective activity of cholesterol, especially in stroke and Alzheimer's disease (AD). In the present study, a protective activity of this lipid in simulated neonatal anoxia was investigated. Rats were subjected to high cholesterol by feeding their dams with a diet enriched with cholesterol. Half of these rats were subjected to anoxia. One and a half months later, the rats were tested for their ability to acquire a spatial memory, one group on the linear maze and the other on the Morris water maze. After these assessments, the level of total plasma cholesterol was measured. Rats from dams subjected to neonatal anoxia on standard diet performed worse than control rats in both types of behavioral experiments, whereas anoxic rats from dams were housed on hypercholesterolemic diet performed as control animals. It suggests that dietetic cholesterol applied by their dams protected rats against cognitive deficits elicited by neonatal anoxia. Furthermore, offspring of anoxic rats housed on standard diet had elevated levels of blood cholesterol in relation to control animals. Generally, anoxia affected the concentration of this lipid much stronger than hypercholesterolemic diet of their dams. It might mean that the anoxia-related rise of cholesterol could be involved in physiological phenomenon being an adaptive response to neurotoxic processes. This concept is discussed in relation to pathological mechanisms in AD.
