THE PROBLEM OF SECONDARY INJURY IN SEVERE TRAUMATIC BRAIN INJURIES AND MODERN PERSPECTIVES ON ITS PATHOGENESIS

Severe traumatic brain injury (TBI) remains a leading cause of death and long-term disability worldwide, particularly among young adults. While the primary insult initiates immediate mechanical damage to neural tissue, it is the cascade of secondary injury mechanisms that significantly contributes to ongoing neurological deterioration. These secondary processes include neuroinflammation, excitotoxicity, oxidative stress, blood-brain barrier (BBB) breakdown, mitochondrial dysfunction, and cerebral edema. Modern research underscores the crucial role of cytokine-mediated inflammatory responses, dysregulated cerebral autoregulation, and glial cell activation in the amplification of neuronal injury. Advancements in molecular biology and neuroimaging have elucidated pathophysiological pathways, such as the involvement of cyclooxygenase-2 (COX-2), matrix metalloproteinases (MMPs), and NLRP3 inflammasome activation in mediating neuronal apoptosis and cerebral edema. Current therapeutic strategies, including multimodal monitoring and neuroprotective interventions (e.g., COX-2 inhibitors, hypothermia, and mitochondrial stabilizers), are aimed at mitigating these secondary injuries. This review synthesizes recent findings (2018–2024) to provide a comprehensive overview of secondary injury pathogenesis in TBI and highlights emerging therapeutic targets that may improve outcomes in critically ill patients.