ause and effect in the relationship between inflammation and cerebral tissue damage. In the rat brain, both experimental subarachnoid hemorrhage and global forebrain ischemia induced upregulation of inflammatory gene pathways, as represented by the transcription factor NFB. Moreover, focal cerebral ischemia caused not only local inflammation but also widespread cerebral inflammation. POCD is a growing and largely underestimated problem without a defined etiology. Globally, experts were focused on discovering risk factors for the occurrence of POCD and developing precautions to reduce its incidence rate, but results have thus far been inconsistent. Meta-regression analyses utilizing the subgroup of studies reporting preoperative mean IL-6 levels suggested that the postoperative level of some inflammatory markers might have contribution to the occurrence of POCD. In Cibelli model, IL-6 plasma levels and transcription in the hippocampus appeared to increase after surgery. IL-6 had facilitating effects on IL-1 in mediating inflammation and causing hippocampal-dependent memory impairment. Hudetz indicated that elevated postoperative IL-6 and CRP concentrations were associated with the subsequent development of short-term and medium-term impairment of cognitive functions after coronary 12411425 7 Inflammatory Markers in POCD: A Meta-Analysis artery surgery. The relationship between inflammation and cognitive deficit was studied in a healthy young population after infusion of IL-6 to simulate the physiological acute-phase response, and the results indicated an explicit decrease in selfreported concentration and cognitive abilities. The metaregression analyses also expressed the same tendency. Assessment of hippocampal expression of the TMS cost proinflammatory 15722457 cytokines IL-6 confirmed that aged mice showed compared to adults embraced higher basal expression of these inflammatory genes in agreement with prior reports that showed aging primes microglial cells. As the global aging progresses, the search for new preventative measures and treatment strategies to maintain higher brain functions throughout life is of major economic and medical importance. In recent years, numerous studies have suggested that multiple strategies, including aerobic exercise, art therapy, and caloric restriction could enhance cognitive fitness. It would improved perioperative brain functional recovery that searching for biomarkers of brain functional reserve and the methods which could enhance it. IL-6 might be a biomarker that could guide the prevention and treatment of POCD. There was growing interest in inflammation-targeted therapeutics. The present meta-analysis examining the role of peripheral inflammatory marks in 
POCD has several methodological limits. The literature search was limited to unstimulated cytokines, NSE, and S-100; however, other inflammatory markers, NF-B) have also been informative. This meta-analysis was also limited by the substantial inconsistency in most comparisons, necessitating the use of random effects models that produced wider confidence intervals for most inflammatory markers.Most studies reported large standard deviations, suggesting substantial unexplained inter-individual variation in inflammatory marker concentrations. Some potential sources of heterogeneity, including assay methodology, age, gender, and medical comorbidity, were investigated. The present study was also limited by the use of a categorical diagnosis of POCD; thus, POCD severity effect