The Role Of TREM1 And TREM2 In Postoperative Cognitive Dysfunction After Total Knee Arthroplasty In Elderly Patients

Objective:Postoperative Cognitive Dysfunction?POCD?is one of the most commom complication in older adults and can have detrimental effects on patients prognosis and quality of life.A large evidence has implicated the roles of neuroinflammation and peripheralinflammation in the pathogenesis of POCD.Triggering Receptor Expressed on Myeloid cells?TREM?play an important role in innate immune system and acquired immune system when its associated with the adaptor molecule DAP12.TREM1,which is reported as a pro-inflammation receptor which interacts with Toll-like receptors?TLR2/4?.In response to the TREM1 activation,the signaling transduction of MAPK and JAK/STAT is activated,ultimately inducing and enhancing the inflammatory reaction.TREM2 is widely known as an inhibitor of the inflammatory response,which is probably via downregulating the signaling protein PI3K/AKT and the expression of ERK1/2.This research is to explore the changes of TREM1 and TREM2after Total Knee Arthroplasty?TKA?and its role in POCD.Methods:A total of 80 ASA grade I-III patients,aged from 65-85 years,who received elective TKA were enrolled in this study.Patients were subjected to 8h food deprivation and 4h water deprivation before surgery,without preoperative treatment.Before placement of spinal anesthesia,all patients were monitored in accordance with current guidelines,including noninvasive blood pressure as well as continuous electrocardiogram?ECG?and pulse oximetry?Spo2?.Spinal anesthesia?midline puncture?was performed in the lateral decubitus position by a staff anesthetist at L3-4,extracted2ml cerebrospinal fluid after successful subarachnoid puncturewith and then injected0.5%Ropivacaine 2.5-3ml,uptake 4L/min mask oxygen during operationl.A sample of5ml peripheral blood was collected by venipuncture from those patients at T₀?before anesthesia induction?,T₁?24h after surgery?,T₂?72h after surgery?.The levels of sTREM1?sTREM2?TNF-?and IL-6 in serum and sTREM1?sTREM2 in cerebrospinal fluid preoperatively were measured by ELISA.mRNA of TREM1?TREM2?IL-6 and TNF-?in every points were measured by RT-PCR.Cognitive function was measured at the day before surgery and at 7d after surgery used Neuropsychological test?NPT?,included:Word Recognition Memory Test,Digit Span Test?Forward and Backward?,Stroop Color-word Interference Test,Digit Symbol Substitution test and Trail Making Test A.We identified patients with POCD using the Z-Score method that was originally used in the international studies of POCD,and then patients was divided into POCD group?P group?and non-POCD group?NP group?.Results:?1?A total of 18 patients with POCD at 7d,the incidence is22.5%.?2?Compared to NP group,the protein levels of sTREM1 in plasma and mRNA in peripheral blood mononuclear cells?PBMCs?were higher in P group at T1 and T2,and the differences had statistical significance?P<0 01 or P<0 05?.?3?The level of TNF-?and IL-6 in POCD group was higher than that in NPOCD group with significant differences?P<0.05?.?4?No significant changes of TREM2 level were found at all time points between groups?P>0.05?.?4?There was a significant correlation between sTREM levels in serum preoperatively and in cerebrospinal fluid?CSF?preoperatively?sTREM1:Pearson r=0.708,P<0.01;sTREM2:Pearson r=0.712,P<0.01?.Conclusion:?1?The level of TREM1 increased in peripheral blood of elderly patients after knee arthroplasty.?2?TREM1 play a role in the pathogenesis of POCD,which is by mediating inflammatory response.?3?There was a significant correlation between sTREM levels in serum preoperatively and in cerebrospinal fluid?CSF?preoperatively.