• Taylor J Orr, Emal Lesha, Alexandra H Kramer, Arba Cecia, John E Dugan, Barrett Schwartz, and Stephanie L Einhaus.
• College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee. Electronic address: Torr2@uthsc.edu.
• World Neurosurg. 2024 May 1; 185: 748874-88.

AbstractTraumatic brain injury (TBI) is a critical public health concern with profound consequences for affected individuals. This comprehensive literature review delves into TBI intricacies, encompassing primary injury biomechanics and the molecular pathophysiology of the secondary injury cascade. Primary TBI involves a complex interplay of forces, including impact loading, blast overpressure, and impulsive loading, leading to diverse injury patterns. These forces can be categorized into inertial (e.g., rotational acceleration causing focal and diffuse injuries) and contact forces (primarily causing focal injuries like skull fractures). Understanding their interactions is crucial for effective injury management. The secondary injury cascade in TBI comprises multifaceted molecular and cellular responses, including altered ion concentrations, dysfunctional neurotransmitter networks, oxidative stress, and cellular energy disturbances. These disruptions impair synaptic function, neurotransmission, and neuroplasticity, resulting in cognitive and behavioral deficits. Moreover, neuroinflammatory responses play a pivotal role in exacerbating damage. As we endeavor to bridge the knowledge gap between biomechanics and molecular pathophysiology, further research is imperative to unravel the nuanced interplay between mechanical forces and their consequences at the molecular and cellular levels, ultimately guiding the development of targeted therapeutic strategies to mitigate the debilitating effects of TBI. In this study, we aim to provide a concise review of the bridge between biomechanical processes causing primary injury and the ensuing molecular pathophysiology of secondary injury, while detailing the subsequent clinical course for this patient population. This knowledge is crucial for advancing our understanding of TBI and developing effective interventions to improve outcomes for those affected.Copyright © 2024 Elsevier Inc. All rights reserved.

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