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Repeated exposure to propofol potentiates neuroapoptosis and long-term behavioral deficits in neonatal rats
- Source :
- Neuroscience Letters. 534:41-46
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- Previous studies have shown that exposure of the immature brain to drugs that block NMDA glutamate receptors or drugs that potentiate GABA(A) receptors can trigger widespread neuroapoptosis. Almost all currently used general anesthetics have either NMDA receptor blocking or GABA(A) receptor enhancing properties. Propofol, a new intravenous anesthetic, is widely used in pediatric anesthesia and intensive care practice whose neurotoxicity on brain development remains unknown. We investigated the effects of neonatal propofol anesthesia on neuroapoptosis and long-term spatial learning/memory functions. Propofol was administered to 7 day-old rats either as a single dose or in 7 doses at concentrations sufficient to maintain a surgical plane of anesthesia. Immunohistochemical studies revealed a significant increase in the levels of caspase-3 in the hippocampal CA1 region after propofol administration. At postnatal day 34, light microscopic observations revealed a significant reduction in neuronal density and apparent morphological changes in the pyramidal cells of rats that had received 7 doses of propofol. These rats showed a longer escape latency/path length, less time spent in the target quadrant and fewer original platform crossings in the Morris Water Maze test. This treatment also produced a remarkable reduction in the levels of excitatory neurotransmitters in the cortex and the hippocampus as measured by high performance liquid chromatography. Repeated exposure to propofol induced exposure-time dependent neuroapoptosis and long-term neurocognitive deficits in neonatal rats. The neurocognitive deficits may be attributed to neuronal loss and a reduction of excitatory neurotransmitter release in the cortex and hippocampus.
- Subjects :
- Male
Time Factors
Excitatory Amino Acids
Morris water navigation task
Apoptosis
Pharmacology
Hippocampal formation
Hippocampus
Rats, Sprague-Dawley
Memory
Intensive care
medicine
Animals
Learning
Maze Learning
Propofol
Cerebral Cortex
Neurotransmitter Agents
Dose-Response Relationship, Drug
business.industry
Pyramidal Cells
General Neuroscience
Glutamate receptor
Neurotoxicity
medicine.disease
Rats
Animals, Newborn
Anesthesia
Anesthetic
NMDA receptor
Female
business
Anesthetics, Intravenous
medicine.drug
Subjects
Details
- ISSN :
- 03043940
- Volume :
- 534
- Database :
- OpenAIRE
- Journal :
- Neuroscience Letters
- Accession number :
- edsair.doi.dedup.....04a06112ea0c4a467fe57d6aa4add48e
- Full Text :
- https://doi.org/10.1016/j.neulet.2012.12.033