This prospective, observational study investigates the impact of repeated general anesthesia exposure on neuroinflammatory biomarkers and neurotrophic factors. The study will enroll 160 adult patients (aged 18-65 years) scheduled for elective cholecystectomy surgery, divided into two groups: patients with no previous general anesthesia exposure (n=80) and patients with at least one or more previous general anesthesia exposures (n=80).

Serum levels of Brain-Derived Neurotrophic Factor (BDNF), Interleukin-1 beta (IL-1β), and High Mobility Group Box 1 (HMGB1) will be measured using ELISA method at two time points: preoperatively (baseline) and 24 hours postoperatively. Cognitive function will also be assessed at both time points.

The primary objective is to evaluate whether multiple exposures to general anesthesia lead to significant differences in serum BDNF, IL-1β, and HMGB1 levels, reflecting changes in neurotrophic balance and neuroinflammatory response. This study aims to provide insights into the potential biochemical mechanisms underlying anesthesia-related cognitive changes and contribute original clinical data to the current literature on general anesthesia safety and neurobiological effects.

Inclusion Criteria:

• Age 18-65 years
• Scheduled for elective cholecystectomy surgery
• Either no previous general anesthesia exposure OR at least one or more previous general anesthesia exposures
• Ability to provide informed consent
• American Society of Anesthesiologists (ASA) physical status I-II

Exclusion Criteria:

• Chronic neurological diseases (Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc.)
• Psychiatric illness requiring medication
• Metabolic syndrome (diabetes mellitus, hypertension, cardiac disease)
• Chronic inflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus, etc.)
• Corticosteroid or immunosuppressive therapy within the last 6 months
• Patients requiring intensive care admission
• Pregnancy or breastfeeding
• Known allergy to anesthetic agents
• Inability to provide informed consent

This study will enroll adult patients aged 18-65 years scheduled for elective cholecystectomy surgery at Malatya Turgut Özal University Training and Research Hospital. Participants will be divided into two groups based on their previous general anesthesia exposure history: (1) patients with no prior general anesthesia exposure (control group, n=80), and (2) patients with at least one or more previous general anesthesia exposures (study group, n=80). Healthy volunteers with no previous surgical or anesthesia history will comprise the control group, while patients with previous surgical procedures requiring general anesthesia will comprise the study group. Both groups will be matched for age and body mass index. Participants with chronic neurological diseases, psychiatric disorders, metabolic syndrome, chronic inflammatory conditions, or recent immunosuppressive therapy will be excluded.

The decision to share individual participant data (IPD) will be made after consultation with the institutional ethics committee and upon completion of primary analyses. Any data sharing will be contingent upon appropriate ethical approval, participant consent provisions, and establishment of a formal data sharing agreement. The final decision will be determined based on ethical, legal, and privacy considerations specific to the Turkish healthcare system and institutional policies.