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Published on: May 12, 2018
Potential mechanism of cell death in the developing rat brain induced by propofol anesthesia
Vesna Pesić1, Desanka Milanović, Nikola Tanić
1Department of Neurobiology, Institute for Biological Research, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.
Insights
Propofol anesthesia can harm the developing rat brain by causing cell death. This study reveals molecular changes, including decreased nerve growth factor (NGF) and activated caspase-3, contributing to neurodegeneration.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Anesthesiology
Background:
- General anesthetics pose risks to developing brains, potentially causing neurodegeneration.
- Previous studies in rats suggest adverse effects of anesthetics on brain development.
Purpose of the Study:
- To investigate the molecular mechanisms underlying propofol-induced apoptosis in the developing rat brain.
- To examine the effects of propofol on nerve growth factor (NGF) and Akt signaling pathways.
Main Methods:
- Propofol anesthesia was administered to 7-day-old (P7) rats.
- Nerve growth factor (NGF) mRNA and protein levels were measured.
- Phosphorylated Akt levels were assessed.
- The extrinsic apoptotic pathway, including tumor necrosis factor (TNF) and caspase-3 activation, was analyzed.
- Neurodegeneration was confirmed using Fluoro-Jade B staining.
Main Results:
- Propofol anesthesia led to down-regulation of NGF mRNA and protein in the cortex and thalamus.
- A decrease in phosphorylated Akt was observed post-propofol treatment.
- The extrinsic apoptotic pathway was activated, evidenced by increased TNF and caspase-3 activation.
- Fluoro-Jade B staining confirmed neurodegeneration in the cortex and thalamus.
Conclusions:
- Propofol anesthesia at a dose of 25mg/kg induces significant molecular changes in the developing rat brain.
- These changes include reduced NGF and Akt signaling, and activation of the extrinsic apoptotic pathway, leading to cell death.
- The findings provide direct evidence of propofol's neurotoxic effects on the developing cortex and thalamus.
Abstract:
Commonly used general anesthetics can have adverse effects on the developing brain by triggering apoptotic neurodegeneration, as has been documented in the rat. The rational of our study was to examine the molecular mechanisms that contribute to the apoptotic action of propofol anesthesia in the brain of 7-day-old (P7) rats. The down-regulation of nerve growth factor (NGF) mRNA and protein expression in the cortex and thalamus at defined time points between 1 and 24h after the propofol treatment, as well as a decrease of phosphorylated Akt were observed. The extrinsic apoptotic pathway was induced by over-expression of tumor necrosis factor (TNF) which led to the activation of caspase-3 in both examined structures. Neurodegeneration was confirmed by Fluoro-Jade B staining. Our findings provide direct experimental evidence that the anesthetic dose (25mg/kg) of propofol induces complex changes that are accompanied by cell death in the cortex and thalamus of the developing rat brain.
