Effects Of Propofol Anesthesia On The Brain Development In Neonatal Rats

Objective:To investigate the effects of propofol on the brain development in neonatal rats and its possible mechanism.Methods Sixty seven-day-old Sprague Dawley rats of either sex in approximately equal numbers, were randomly divided into three groups (n=20, each): rats in group C were intraperitoneally injected with 0.9% normal saline (NS) 7.5 ml/kg once per day for seven days; group P₁ were injected NS 7.5 ml/kg once per day for six days and propofol 75 mg/kg (7.5 ml/kg) on the seventh day; group P₂ were injected propofol 75 mg/kg once per day for seven days. Blood glucose were tested in two rats of each group with tails cut off 3 hours after the last intraperitoneal injection; and six rats of each group were decapitated 5 hours after the last intraperitoneal injection for determination of caspase-3 (CPP3) expression with immuno-histochemistry. Spatial learning and memory function were evaluated using Morris water maze when the rats were 4 weeks old. The rats were decapitated immediately after the tests. Cortex and hippocampus of six rats of each group were isolated for determination of aspartate (Asp),glutamate (Glu),glycine (Gly) andγ-aminobutyric acid (GABA) contents with high efficiency liquid chromatography (HPLC), and the others were decapitated for microscopic examination. Results1. SpO₂ and blood glucose level in three groups were observed and keeped in normal. There were no significant differences in body weight among the three groups.2. In CA1 region of hippocampus of rats in group C, activated CPP3 immunocytochemistry staining revealed a sparsely scattered pattern of baseline physiological cell death. Compared with group C, CPP3 expression were significantly increased in both group P₁ and P₂ (P <0.05). It in group P₂ was more obvious than that in group P₁ (P <0.05).3. Pathologic results of the three groups revealed that the structure and the shape of pyramidal neurons in hippocampus were keeped in normal in group C and P₁; while pyramidal cell layer lined up in disorder and abnormal shape of pyramidal neurons were discoved in group P₂. Compared with group C, the number of pyramidal neurons were decreased in both group P₁ and P₂, especially in group P₂ (P <0.05).4. Rats of group P₁ did not significantly differ from group C in the contents of amino acid transmitters in cortex and hippocampus. It was found that the Asp content in hippocampus, the Glu contents and Glu/GABA ratio both in cortex and hippocampus in group P₂ were significantly lower than in group C and P₁ (P <0.05). But there were no significant differences in Gly and GABA contents both in cortex and hippocampus among the three groups (P >0.05). 5. When tested in the Morris water maze, rats of group C and P₁ performed similarly. Compared with C and P₁ groups, escape latency and path length of rats in group P₂ were significantly increased from the third day of training test (P <0.05), while the time searching platform in target quadrant and the times crossing over the former platform location were decreased (P <0.05). There were no significant differences in swimming speed among the three groups (P >0.05).Conclusion1. Our findings indicate that exposure of neonatal rats to propofol triggers apoptosis in the hippocampus, resulting in deletion of neurons to different degree from the developing brain; but pyramidal cell layer lined up in disorder and the abnormal shape of pyramidal neurons are observed only in rats repeatedly injected propofol.2. Rats treated with multiple doses of propofol show significant decreases in excitatory amino acids transmitters contents and Glu/GABA ratio in brain as juvenile.3. Rats exposed to multiple doses of propofol display deficits in learning and memory capabilities as juvenile, which may be related to neuron deletion caused by over apoptosis and a decrease of excitatory amino acid transmitters contents in brain.