Background: Traumatic Brain Injury (TBI) consists of two processes primary injury and secondary injury. Secondary injury in TBI involves many factor of molecular and cellular responses to the primary impact. All of these factors culminate in cellular dysfunction and cell death via necrotic and more apoptotic. These downstream molecular and cellular processes in the secondary injury are the focus of many pre-clinical and clinical therapeutic studies. The spatiotemporal distribution of S-100B, IL-6, AQP4 productions in secondary injury are some key marker of acute feature after TBI pathophysiology. By examining changes of this protein in these processes, we can expect to identify novel approaches to TBI intervention. Hypotheticly, posttraumatic suppression of the hypothalamic-pituitary-adrenal axis and an increase in cytokine-mediated peripheral aromatase activity, leading to an imbalance in sex steroid estrogen, progesterone, and testosterone serum levels, have been interest for precise understanding of that mechanisms involved. We treatment analyzed serum biomarkers (S100-B, IL-6, AQP4) as part of a randomize placebo-controlled of progesterone in patients with severe TBI (sTBI), and analyzed the long-term predictive value of these biomarkers on the dichotomized Glasgow Outcome Scale (GOS) score at 3 months. Method: This study was part of a prospective, outcome-assessor–and statistician-blinded, randomized, placebo- controlled trial of progesterone. The population age 15 – 60 years patients with severe TBI (sTBI), (Glasgow Coma Scale (GCS) score 4–8, who presented at our care trauma center, Central Hospital Dr Sutomo Surabaya within 24 hours after injury. We obtained approval from institutional ethics committee prior to the trial. Of 40 patients with sTBI, we serially analyzed 3 serum biomarkers S-100B, AQP4, and IL-6. We analyzed the long-term predictive value of serum biomarkers on dichotomized GOS score of 3 months. The serum levels of S-100B, IL-6, AQP4 were determined using a sandwich ELISA technique. The samples for the determination of these biomarkers were taken at the day I (24 hours), immediately after randomization and before Progesterone given intramuscular 1 mg/kgBW single dose, and then day IV (96 hours) later. Using IBM SPSS Statistic software version 22, analysis for 24 hours, 96 hours, and average serum biomarkers stratified according to outcome (The dichotomized GOS) was performed. Results: The serum levels S-100B, AQP4 and IL-6 were across the dichotomized GOS groups at 3 months in both groups. GOS 3 months maked two category: Poor outcome (label 1) for GOS score 1 – 3 and good outcome (label 2) for GOS 4 – 5. Binary logistic regression result showed all value biomarker significant model to prediction the GOS dichotomy. Analysis to prediction from good outcome to poor outcome (to right axis direction) we have the simulation equation. unfav. = X good - X poor. In the control group: S100B was increase, AQP4 was decrease and IL-6 no change. To analysis effect of progesterone as intervention group we found S-100B was extremely high increased that means progesterone indirectly can reduce neuronal injury. AQP4 and IL-S was decrease compare to control, that mean possibly progesterone have effect modulating up regulation in AQP 4 to inhibit neuroinflamation. Conclusion: Serial monitoring of S-100B, IL-6 and AQP4 serum levels could aid in prognostication in patients with sTBI. S-100B is the best good accuracy for predict outcome. Progesterone have an effect in change of S-100B serum level expression that involve in neuronal injury, and the process of cerebral edema (modulating AQP4 link to IL-6). However, in this study Progesterone had no benefit in overall clinical outcome (GOS dichotomy 3 months).
