Darvish, Kurosh2025-01-232025-01-232024-12http://hdl.handle.net/20.500.12613/10948Traumatic brain injury (TBI) is a major health concern, with mild TBI (mTBI) being the most common type and frequently linked to long-term neurological issues. Studying mTBI is essential to improve prevention, diagnosis, and treatment strategies for affected individuals.This dissertation explores the biomechanical and biological impacts of mTBI induced by blast exposure and rapid acceleration, focusing on both experimental replication and finite element (FE) modeling. In experimental studies, using a custom-built shock tube, this study replicated blast-induced TBI (bTBI) in rats, examining the effects of single and multiple blast exposures on behavioral and histological outcomes. Behavioral evaluations using Rotarod and Open Field tasks, along with histological markers (GFAP, Iba-1, and tau protein), demonstrated that multiple blast exposures resulted in more severe motor deficits and neuroinflammatory responses than single exposures. This highlights cumulative injury risks. To address repetitive rmTBI as observed in sports and military settings, a novel Whole Body Deceleration (WBD) model, based on rapid acceleration-deceleration, was introduced. This model induced rmTBI in rats, with motor function and anxiety-like behaviors assessed alongside histological analyses of microglial activation (Iba-1) and inflammatory markers (TLR4 and TNF-α). Results indicated increased microglial activation and TLR4 expression, with notable motor impairments in the acute post-injury phase (7 days). These findings underscore the complex neuroinflammatory responses associated with rmTBI. Additionally, the long-term (21 days) effects of WBD and the impact of different injury repetition patterns were evaluated. The Novel Object Recognition task was incorporated alongside previous behavioral assessment tools to assess memory function. Over the long term, WBD led to increased impulsivity in rats, with repetition patterns influencing behavioral trends. However, no persistent memory deficits were observed over this period. Furthermore, we investigated O-1966 (CB2) as a therapeutic option for bTBI and both O-1966 and KLS for WBD. CB2 demonstrated a reduction in neuroinflammation following bTBI in the acute phase. KLS and CB2 showed no conclusive evidence of improving anxiety or memory deficits following WBD in the long term. This study developed a validated 3D FE model of a shock tube to simulate blast wave effects on a rat’s head, examining key parameters like peak overpressure and positive phase duration. The model effectively replicates blast conditions in the experiments, advancing our understanding of bTBI mechanisms. Lastly, a comparative biomechanical analysis was conducted between our blast-induced and acceleration-induced mTBI using FE simulations. Key metrics such as intracranial pressure, pressure impulse, von Mises stress, maximum principal strain, and stress power (time derivative of internal energy) revealed distinct injury patterns. The blast model centralized the energy, leading to higher shear stress and pressure, indicating a more diffuse and severe injury profile. Conversely, the acceleration model demonstrated a more symmetric distribution of energy, especially between Coup and Contrecoup regions, suggesting a localized injury effect.166 pagesengIN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.http://rightsstatements.org/vocab/InC/1.0/BiomechanicsMechanical engineeringBioengineeringBlastFinite element simulationMildRapid accelerationTBITraumatic brain injuryText159532025-01-21Vafadar_temple_0225E_15953.pdf