Relationship Between Neuronal Excitability And Neuronal Toxicity Of Sevoflurane In Mice

Objective: To investigate the excitability of sevoflurane anesthesia on mice neurons and its effect on neuron apoptosis.Methods: Mouse sevoflurane inhalation anesthesia excitation model was established,and video tracking software was used to record the mouse movement within 30 minutes after anesthesia,and observe the excitement of sevoflurane anesthesia.The transient expression of c-fos protein was used as the neuronal activation marker to observe the brain regions stimulated by sevoflurane anesthesia.TUNEL was used to label neuronal apoptosis and observe the anesthetic neurotoxicity of sevoflurane.Mice with sevoflurane induced hyperactivity were sacrificed by decapitating,and continuous coronal sections 30 microns thick were cut with a frozen slicing machine.Immunofluorescence staining was used to detect neuronal activation and cell apoptosis in each brain region of the mice,and to observe whether the two regions overlapped.Western Blot(Western blot)was used to detect phosphorylated Tau(Ta U-PS202 /Tau-PT205)protein in the whole cerebral cortex of young rats after7 hours of anesthesia.The control group was injected intrapitoneal with dexmedetomidine(5ug/kg)to enhance the anesthetic effect.The inhibitory effect of dexmedetomidine on nerve excitability and its neuroprotective effect were observed.Intrapitoneal injection of modafinil(50mg/kg)antagonized the anesthetic effect,and observed the anesthetic effect of modafinil sevoflurane,but increased the effect of neurotoxicity.Results:There was no significant difference in the travel distance between control group and blank group(P > 0.05).The moving distance of the mice was different under the concentration of 1%,1.5%,2.0%,2.5% and 3% of sevoflurane,and the moving distance of the mice under the concentration of 1.5% sevoflurane was longer.Compared with the normal saline group,intrapitoneal injection of dexmedetomidine(5ug/kg)reduced the distance mice moved under sevoflurane anesthesia(p < 0.0001)and significantly reduced the number of c-fos positive cells in the prefrontal cortex and temporal cortex of mice(P < 0.001).Decreased the number of TUNEL positive cells in the prefrontal cortex and temporal cortex of mice(P < 0.001);Intrabitoneal injection of modafinil(50mg/kg)increased the distance of movement under sevoflurane anesthesia in mice(p < 0.001),the number of c-fos positive cells in the prefrontal cortex and temporal cortex(P < 0.001),and the number of TUNEL positive cells in mice(P < 0.001).There was no difference in the expression of phosphorylated Tau protein in the brain of rats without sevoflurane anesthesia(P > 0.05).Compared with the normal saline group,intraperitoneal injection of dexmedetomidine(5ug/kg)could reduce the phosphorylated Tau protein content,and the difference was significant(p < 0.0001).Intrabitoneal injection of modafinil(50mg/kg)increased phosphorylated Tau protein expression(p < 0.001).Conclusion: Sevoflurane anesthesia caused excitement and agitation in mice,and the activation of neurons in the brain increased,and the activation of neurons in the cortical region of mice with increased excitatory hyperactivity was more obvious.Prolonged anaesthesia could increase apoptosis.Dexmedetomidine can enhance the sedative effect of anesthetics,reduce the expression of C-FOS,reduce cell apoptosis,and reduce the phosphorylated Tau protein content in the cerebral cortex of mice.Modafinil can shorten the recovery time of righting reflex,increase the activity of mice,increase the expression of C-FOS,increase cell apoptosis,and increase the phosphorylated Tau protein content in the cerebral cortex of mice.The areas with more apoptosis(TUNEL)overlapped with the areas of neuronal activation(C-FOS)(prefrontal cortex and temporal cortex).