Combination Determination Of Brain-derived Neurotrophic Factor And High-Sensitivity C-Reactive Protein Predicts The Post-Stroke Depression In Patients With Ischemic Stroke

Background and ObjectivePost-stroke depression(PSD)is the most common neuropsychiatric complications after stroke,which aggravates the mortality,recurrence and disability rates of stroke patients.At present,the pathogenesis of PSD is still unclear.Studies have shown that the occurrence of PSD is related to nerve regeneration and neuroinflammation after stroke.A number of studies have shown that brain-derived neurotrophic factor(BDNF)and high-sensitivity C-reactive protein(hs-CRP)is closely related to the occurrence of PSD,but the effects of BDNF and hs-CRP on PSD have been studied separately before,the combined effect of the two has not been reported yet.Therefore,this study aims to explore the predictive value of plasma BDNF combined with hs-CRP and the risk factors that affect the occurrence of PSD,so as to identify high-risk patients with PSD as soon as possible and take early intervention and treatment to improve the prognosis of stroke patients.MethodsThis study is a prospective study.230 patients with acute ischemic stroke were continuously admitted to the Department of Neurology of the First Affiliated Hospital of Zhengzhou University from March 2019 to September 2019 within 14 days of their first onset.According to the inclusion and exclusion criteria 7 cases were excluded,7 cases were lost to follow-up,and 216 cases were finally enrolled.At 6 months follow-up,patients were divided into post-stroke depression group and non-depression group according to the 17-item Hamilton Depression Scale(HAMD-17)score,and HAMD scores>7 indicated a diagnosis of PSD.Enzyme linked immunosorbent assay(ELISA)was used to assess plasma BDNF levels and hs-CRP levels on admission,baseline data and relevant laboratory test results were compared between the two groups of patients.Binary Logistic regression,Spearman correlation analysis and receiver operating characteristic curve(ROC)were used to statistically analyze the relevant data of the two groups of patients.At the 6-month follow-up,10 patients in each of the PSD group and the NPSD group with matching baseline data were selected.High-throughput sequencing was used to analyze the differential expression profile of miRNA between the two groups.Using bioinformatics methods and related analysis software to predict target gene,GO enrichment and KEGG functional enrichment analysis.Results1.A total of 216 acute stroke patients were enrolled in this study,including 154 males(71.2%)and 62 females(28.7%);they were 26-92 years old,with an average age of 59.7 years.At the 6-month follow-up,according to the HAMD scores>7 divided into depression group and non-depression group,of which 72 cases were in PSD group and 144 cases were in NPSD group.The incidence of PSD was 33.3%.2.The plasma BDNF of the PSD group was significantly lower than that of the NPSD group,and the plasma hs-CRP of the PSD group was significantly higher than that of the NPSD group.The differences were statistically significant(P<0.001).Multivariate logistic regression analysis of the relationship between each factor and PSD showed that the low level of BDNF at admission(OR=-0.534,95%CI:0.491-0.700,P<0.001)and the high level of hs-CRP(OR=2.325),95%CI:1.496-3.612,P<0.001)is a risk factor for PSD at 6 months after acute ischemic stroke.3.The area under curve(AUC)of the combined detection of plasma BDNF and hs-CRP to predict PSD was 0.906,and the difference was statistically significant(P<0.001).The predictive value of the combined result was higher than the predictive value of BDNF(AUC=0.874)or hs-CRP(AUC=0.760).4.After analysis using bioinformatics and other methods,the expression levels of miR-140-5p,miR-30a-5p,and miR-363-5p in the PSD group compared with the non-PSD group were the most significantly different(P<0.001).miR-30a-5p and miR-363-5p are significantly up-regulated,and miR-140-5p is significantly down-regulated.5.The target gene prediction and functional enrichment analysis results showed that the KEGG enrichment analysis mainly focused on the enzyme signal transduction pathway(MAPK),hippocampus signaling pathway and neurotrophic signaling pathway.Conclusions1.Low levels of BDNF and high levels of hs-CRP on admission may be risk factors for PSD 6 months after stroke.Combined detection of plasma BDNF and hs-CRP can be used as a reliable indicator to predict the occurrence of PSD.2.Bioinformatics analysis shows that the target proteins of miR-140-5p,miR-30a-5p and miR-363-5p are mainly involved in neurotrophic signal transduction,Hippo signaling pathway,MAPK and other biological processes and related to neuroplasticity and inflammation.We speculate that these differentially expressed miRNAs may cause a variety of changes in biological characteristics by regulating the expression of a series of downstream target genes,which is involved in the occurrence and development of PSD.