Post-operation cognitive dysfunctions, related to mild manifestations of neurological pathology occuring after surgery, represent an important challenge for both fundamental and clinical medicine. The underlying phenomena of neuroinflammation are still poorly understood and discutable. The studies in immunopathogenesis of neuroinflammation may help in understanding the development of pathology and suggest ways to solve this problem. A special role for implementation of this process belongs to neuropeptides. Objective: to characterize immunopathogenesis of neuroinflammation in the individuals with immunocompromised state induced during aorto-coronary bypass surgery. A total of 110 patients with ischemic heart disease who underwent myocardial revascularization under extracorporeal circulation conditions were examined. Pathological neuroinflammation was recognized by development of postoperative cognitive dysfunction based on changing results of the cognitive examination (Montreal scale, MoCa test). The patients were tested before intervention, and on day 7 after surgery. According to the test results, all the patients were divided into 2 groups: (1) without signs of postoperative cognitive dysfunction and (2) with the mentioned signs. Venous blood was collected four times, on the day of surgery before the intervention, immediately after the surgery, 24 hours later, and on the 7th day after surgery. S100b and BDNF contents were determined in the venous blood serum. The baseline level of the S100b protein in the study groups did not differ from the reference values. After surgery, an increase in S100b was observed in both groups, but in patients with emerging postoperative cognitive dysfunction, these indexes were significantly higher. Despite a tendency for stabilization, the increased level of neuropeptides persisted 24 hours after the surgery; on the 7th day, the index was within the reference values, but in the 1st group it was lower than in the 2nd group. Prior to the operation, the BDNF level was significantly higher in the patients from group 1, compared with group 2. In the second group, the index was lower than the values obtained from the control group volunteers. After surgery, the values of BDNF in blood serum showed some differences: immediately after surgery, the level of neuropeptide was higher in patients without cognitive dysfunction. On day 7, the level of BDNF was within reference values, but in patients from group 2, the values were higher than in group 1.
With regard of post-surgical cognitive disturbances, an active search for biological markers of these neurological complications is performed. We have studied the contents of NSE, IL-6, TGF-β1, MMP9 and TIMP1 in blood serum of these patients. The study included 110 patients after aortal-coronary bypass surgery using extracorporeal blood circulation. Splitting into separate groups was based on the test scores, according to Montreal Cognitive Assessment Scale prior to surgery and on day +7 after the intervention: (I) patients without complications ( 3 points); (II) patients with post-surgical cognitive impairment ( 3 points). The comparison group (III) included 35 healthy subjects. Evaluation of NSE, IL-6, TGF-β1, ММP9 and TIMP1 in blood serum was performed by means of ELISA technique (RD Systems, USA). The data were expressed as pg/ml, or ng/ml. Blood sampling was made at 4 terms: before surgery, just after intervention, 24 h later, and on day 7 after the surgery.The patients from group II showed higher NSE levels, except of 7 days after surgery when it became similar to other groups. Increased IL-6 levels were found in the patients from group II at all terms after surgery. Decreased concentration of TGF-β1 was found in the II group prior to operation, 24 h and 7 days after the surgery. However, just after surgery, this index was increased, and its values barely differed from results of groups I and III. Studies of MMP9 showed significant differences between groups I and II only on day +7 after. However, lower MMP9 content was detected in the patients from I and II groups before surgery compared to group III. TIMP1 values showed gradual increase over the observation period, but did not differ between groups I and II. In the patients from group II, an increased content of NSE and IL-6 was revealed, along with low TGF-β1 levels and decreased ММP9/TIMP1 ratio over early postsurgical period, thus suggesting possible role of innate immunity dysfunction in pathogenesis of postsurgical cognitive impairment.
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