Abstract
Purpose: To investigate the effect of propofol on brain development in neonatal mice and long-term neurocognitive impact in adult mice.Method: The offspring of female C57Bl/6 and male CD-1 mice were administered propofol at concentrations of 2.5 and 5.0 mg/kg (treatment group) or normal saline (control) on postnatal day 7. Thereafter, histological and immunohistochemical examinations were performed on the mice brain. Apoptotic assay, neuronal nuclei antigen immunohistochemistry (to assess neuron density), and behavioral and neurocognitive tests were conducted on the adult mice.Results: Propofol induced cellular degeneration and apoptosis in the brains of neonatal mice. It also modulated physiological parameters (pH, PO2, glucose and lactate), among which decreased blood glucose might be associated with cellular degeneration in the brain. Propofol also caused long-term neuronal deficits in adults, which showed impaired neurocognitive functions. Upon reaching adulthood, propofol-treated mice showed slow learning response and poor memory compared to controls.Conclusion: Propofol causes neurodegeneration in neonatal mice and has long-term neurocognitive consequences in adults, indicating that the use of propofol anesthetics in neonates requires careful consideration.Keywords: Anesthesia, Apoptosis, Brain injury, Neonate, Neurodegeneration, Propofol
Highlights
Several classes of anesthetic and sedative agents, such as benzodiazepines, barbiturates, ketamine, propofol, and etomidate, have been used in infants and children
Effects of propofol on morphological structures in the brains of neonatal mice degenerative effects of propofol on the morphology of brain segments increased in a dose-dependent manner
Our findings suggest that propofol alone may not be a suitable anesthetic in clinical and surgical procedures for neonates
Summary
Several classes of anesthetic and sedative agents, such as benzodiazepines, barbiturates, ketamine, propofol, and etomidate, have been used in infants and children. At P7, 12 mice (3 from each group) were exposed to 12 h of either NS (controls) or propofol (each treatment group) They were sacrificed and their brains were excised for histological examination by staining with hematoxylin and eosin (HE). At P7, 12 more mice (3 from each group) were exposed to either NS (controls at interval of 12 h) or propofol (5.0 mg/kg at intervals of 3, 6, and 12 h) They were sacrificed and their brains were excised for immunohistochemical (IHC) analyses of apoptosis. The TUNELpositive regions were observed under a light microscope (40×) to score TUNEL-positive cells in brain sections (per mm2); data are presented as the percentage of positive cells compared to controls. All statistical calculations were performed using SPSS v.17, and p < 0.05 was considered statistically significant
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