NEUROINFLAMMATION AS A PROGNOSTIC DETERMINANT IN SEVERE TRAUMATIC BRAIN INJURY

Abstract

This study analyzes the pathophysiological architecture of neuroinflammation in moderate to severe Traumatic Brain Injury (TBI), elucidating the mechanisms of secondary injury and their correlation with prognostic biomarkers and clinical outcomes. Through a narrative literature review, the transition from the reductionist paradigm to systems biology in contemporary neuroprotection was investigated. The secondary cascade is established as a multisystemic process in which pyroptosis, the formation of neutrophil extracellular traps (NETs), and activation of the complement system act synergistically to exacerbate cytotoxic and vasogenic edema. Structural biomarkers, such as glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), in addition to specific cytokines such as IL-6 and IL-1β, emerge as potential predictors of severity, although phenotypic heterogeneity and the absence of universal cutoff values limit their immediate clinical applicability. Evidence indicates that the persistence of a chronic inflammatory state constitutes one of the main determinants of late mortality and persistent cognitive decline observed in survivors. The historical failure of single-target therapies reinforces the need for integrated multimodal interventions. In this context, the management of severe TBI requires abandoning nonspecific immune blockade strategies in favor of selective immunomodulation. Precision medicine, guided by individual biological stratification and understanding of the temporal windows of inflammation, emerges as one of the main scientific frontiers to mitigate morbidity and mortality and optimize long-term functional recovery, offering a personalized approach to a markedly heterogeneous pathology.