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Cardiopulmonary Bypass Induces Differential Neuroregenerative, Inflammatory, and Oxidative Stress Responses

Year: 2026

Type: article

Abstract: Background: Cardiopulmonary bypass (CPB) is a fundamental technique in cardiac surgery; however, it is associated with systemic inflammation, oxidative stress, and adverse postoperative outcomes, including cognitive dysfunction.The pathophysiological mechanisms underlying these complications are not fully understood.Although both traditional and newly identified inflammatory markers have been studied, data on perioperative changes in neuronal plasticity and regeneration markers, such as growth-associated protein 43 (GAP43) and neuregulin-1 (NRG1), remain limited.This study aimed to evaluate preoperative and postoperative levels of GAP43 and NRG1 in patients undergoing CPB and to compare them with markers of oxidative stress, systemic inflammation, and neurological inflammation. Materials and Methods:A total of 41 patients (32 males, 9 females) undergoing elective cardiac surgery with CPB were enrolled.Peripheral blood samples were collected pre-and postoperatively.Serum levels of GAP43, NRG1, brain-derived neurotrophic factor, and osteoprotegerin (OPG) were measured by enzyme-linked immunosorbent assay.Oxidative stress was assessed using total oxidant status (TOS) and total antioxidant status (TAS).Protein expression of sirtuin 2 (SIRT2) and C-X3-chemokine ligand 1 (CX3CL1) was analyzed by Western blotting.Data normality was evaluated with the Shapiro-Wilk test, and appropriate parametric or non-parametric tests were used for paired comparisons.Results: Postoperative GAP43 levels decreased (p < 0.05), and the decrease was more pronounced in males.NRG1 showed no overall change but exhibited sex-specific trends, decreasing in females and increasing in males.OPG increased only in males, while TOS increased and TAS remained unchanged in both groups.Western blot analysis showed a loss of SIRT2 expression and an induction of CX3CL1.Conclusion: CPB induces oxidative stress, neuroinflammation, and disruption of neuroregenerative processes.GAP43, a marker of neuronal plasticity, decreases postoperatively, particularly in males, whereas NRG1 shows a sex-dependent response.Combined assessment of GAP43, NRG1, and inflammatory and oxidative-stress markers may help predict postoperative neurological dysfunction and guide future protective strategies.

Source: Hamidiye Medical Journal

DOI: 10.4274/hamidiyemedj.galenos.2026.66376