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Neuroprotective Effect Of Ac-FLTD-CMK In A Mice Model Of Traumatic Brain Injury And Predictive Value Of Blood Glucose/Potassium Ratio In Prognosis Of Patients With Traumatic Brain Injury

Posted on:2022-08-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:P F WangFull Text:PDF
GTID:1484306554487414Subject:Surgery
Abstract/Summary:PDF Full Text Request
Part One Ac-FLTD-CMK inhibits pyroptosis and exerts neuroprote ctive effect in a mice model of traumatic brain injuryObjective:Pyroptosis has been reported to contribute to the traumatic brain injury(TBI)process.Ac-FLTD-CMK is a newly synthesized pyroptosis inhibitor.However,whether Ac-FLTD-CMK inhibits pyroptosis and plays a neuroprotective role after TBI is unknown.The present study aimed to determine the effects of Ac-FLTD-CMK on TBI in a mouse model.Methods: Male C57BL/6 mice were randomly divided into sham,TBI + vehicle,and TBI + Ac-FLTD-CMK groups.TBI was induced using a weight-drop apparatus.Intraventricular injection of Ac-FLTD-CMK was performed 30 min after TBI.Caspase-1,caspase-11,gasdermin-D(GSDMD),and caspase-3 expression in the peri-contusional cortex were assessed by western blotting.Interleukin-1?(IL-1?)and interleukin-18(IL-18)expression in the peri-contusional cortex were measured using ELISA.Behavioral experiments,brain water content assessment,evans blue extravasation measurement,lactate dehydrogenase(LDH)release evaluation,and terminal deoxynucleotidyl transferasemediated d UTP-biotin nick end labeling staining were also performed.Results:Ac-FLTD-CMK administration significantly downregulated caspase-1 p20,caspase-11 p20,GSDMD N-terminal,IL-1?,and IL-18 expression;reduced LDH release;alleviated neuronal death;attenuated brain edema and blood-brain barrier damage;and improved neurobehavioral function.Conclusions: Ac-FLTD-CMK treatment suppresses pyroptosis and protects mice against TBI.Part Two Predictive value of blood glucose/ potassium ratio in prognosis of patients with moderate and severe traumatic brain injuryObjective:Many blood biomarkers are helpful in predicting the prognosis of traumatic brain injury(TBI),but few are widely used clinically.The aim of this study was to investigate the value of serum glucose/potassium ratio in predicting the outcome of patients with moderate and severe TBI.Methods: One hundred and two patients with moderate and severe TBI admitted to the department of neurosurgery of Hebei General Hospital from 2019.7 to 2020.9 were included in our study.The clinical data,laboratory data,and the protein concentration of caspase-1 and IL-? in the serum were analyzed by univariate and multivariate logistic regression analysis to determine the independent risk factors of the outcome of TBI,and the receiver operating characteristic(ROC)curve was drawn to evaluate the value of independent risk factors in predicting the outcome of TBI.Results:Univariate logistic analysis showed that the admission Glasgow coma scale(GCS),serum glucose,serum potassium,and serum glucose/potassium ratio were the risk factors of worse prognosis of patients with moderate and severe TBI.Multivariate logistic analysis demonstrated that the admission GCS and serum glucose/potassium ratio were the independent risk factors of worse outcome in moderate and severe TBI.ROC curve analysis showed that the area under the ROC curve(AUC)of serum glucose/potassium ratio was 0.75,and the AUC of GCS was 0.791,suggesting a similar predictive value for both indicators.Conclusions: Serum glucose/potassium ratio is a valuable predictor of outcome in patients with moderate and severe TBI,which is helpful for clinicians to develop individualized treatment strategies in the early stage.
Keywords/Search Tags:Ac-FLTD-CMK, Neuroinflammation, Pyroptosis, Traumatic brain injury, Serum glucose, Serum potassium, GCS score, Prognosis
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