The brain is a complex organ and its response to the mechanical loads at all strain rates has been nonlinear and inelastic in nature. Split-Hopkinson Pressure Bar (SHPB) high strain rate compressive tests conducted on porcine brain samples showed a strain rate dependent inelastic mechanical behavior. Finite Element (FE) modeling of the SHPB setup in ABAQUS/Explicit, using a specific constitutive model (MSU TP Ver. 1.1) for the brain, showed non-uniform stress state during tissue deformation. Song et al.’s assertion of using annular samples for negating inertial effects was also tested. FE simulation results showed that the use of cylindrical or annular did not mitigate the initial hardening. Further uniaxial stress state was not maintained is either case. Experimental studies on hydration effects of the porcine brain on its mechanical response revealed two different phenomenological trends. The wet brain (~80% water wt. /wt.) showed strain rate dependency along with two unique mechanical behavior patterns at quasi-static and high strain rates. The dry brain’s (~0% water wt. /wt.) response was akin to the response of metals. The dry brain’s response also observed to be strain rate insensitivity in its elastic modulus and yield stress variations. Uncertainty analysis of the wet brain high strain rate data revealed large uncertainty bands for the sample-to-sample random variations. This large uncertainty in the brain material should be taken into in the FE modeling and design stages. FE simulations of blast loads to the human head showed that Pressure played a dominant role in causing blast-related Traumatic Brain Injury (bTBI). Further, the analysis of shock waves exposed the deleterious effect of the 3-Dimensional geometry of the skull in pinning the location of bTBI. The effects of peak negative Pressure at injury sites have been attributed to bTBI pathologies such as Diffuse Axonal Injury (DAI), subdural hemorrhage and cerebral contusion.