The effects of blast-induced traumatic brain injury on brain cellular mechanics and differentiation.

Abstract

Blast-induced traumatic brain injury (bTBI) causes significant disruptions in cellular and subcellular structures within the central nervous system (CNS) when an extremely large force is applied. The corresponding changes in biomechanical properties and cellular functionalities of neuronal and glial cells due to bTBI remain largely unexplored. In this work, high blast overpressures (BOPs) of 14.5 psi (single shockwave) and 29.0 psi (double shockwave) were applied to adult hippocampal progenitor cells (AHPCs) in two different directions (overpressure applied from 'top-to-bottom' and 'bottom-to-top' direction on the cell culture petridish). The resultant alterations in structural, nanomechanical, and viscoelastic properties as well as cellular survival, proliferation, and differentiation were analyzed using atomic force microscopy (AFM) and immunocytochemistry (ICC). Double shockwave exposure from 'bottom-to-top' direction yielded reduced Young's modulus, surface roughness, and viscosity, causing significant actin cytoskeletal disruptions compared to 'top-to-bottom' direction. ICC results demonstrated that double shockwave exposure from 'top-to-bottom' direction caused populations of oligodendrocytes and immature neurons to decrease, while 'bottom-to-top' double shockwave exposure caused an increase in the percentage of immature neurons as shown by increased TuJ1-immunoreactivity which is interpreted as evidence that cells have committed to a neuronal lineage and entered an immature/early neuronal stage. These findings emphasize the interplay among cellular differentiation, mechanics, and resilience of neuronal and glial cells to trauma in bTBI aftermath.