Temporal Dynamics of Inflammatory, Glial, and Metabolic Biomarkers Following Severe Diffuse Traumatic Brain Injury in a Rat Model

<b>Background:</b> Traumatic brain injury (TBI) initiates a complex sequence of inflammatory, glial, and metabolic events that evolve dynamically and contribute substantially to secondary brain injury. This study aimed to characterize the temporal serum dynamics of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), glial fibrillary acidic protein (GFAP), and insulin following severe diffuse TBI in a rat model, with the goal of delineating the coordinated progression of inflammatory, astroglial, and metabolic responses. <b>Methods:</b> Severe diffuse TBI was induced in adult male Sprague-Dawley rats using the Marmarou weight-drop model. Animals were randomized into five groups (sham, 1 h, 6 h, 24 h, 72 h; n = 10 per group). Serum TNF-α, IL-6, GFAP, and insulin levels were quantified using ELISA assays. Group differences were assessed using one-way ANOVA with Tukey's post hoc test or Kruskal-Wallis analysis with Dunn's correction where appropriate. Results were expressed as mean ± SD. <b>Results:</b> TNF-α demonstrated a biphasic pattern, declining at 6 h before peaking significantly at 24 h (<i>p</i> < 0.05) and subsequently decreasing at 72 h. IL-6 exhibited mild suppression at 6 h followed by a significant secondary elevation at 24 h (<i>p</i> < 0.05), with persistently elevated levels at 72 h. GFAP showed delayed kinetics, decreasing at 6 h but rising progressively to a peak at 24 h, consistent with subacute astroglial activation. Insulin levels declined at 6 h and increased significantly at 24 h and 72 h (<i>p</i> < 0.05), indicating evolving metabolic adaptation. Overall, cytokine activity preceded glial and endocrine changes, revealing a sequential inflammatory-glial-metabolic cascade. <b>Conclusions:</b> This study delineates the temporal serum profiles of TNF-α, IL-6, GFAP, and insulin after severe diffuse TBI, revealing a coordinated transition from acute inflammation to astroglial activation and metabolic adaptation. These results support the utility of multimodal biomarker panels for phase-specific characterization of secondary injury and identify GFAP and IL-6 as promising subacute markers with translational relevance. The findings should be interpreted as descriptive temporal patterns rather than mechanistic evidence, pending confirmation with complementary molecular analyses.