Engineering approaches to investigate the pathophysiology of brain

Abstract

Brain pathophysiology has been traditionally studied by the biochemical approaches, and recent advances in engineering have led to new perspectives in solving problems in biomedical science. In particular, the physicochemical environment has known to closely interact with the development of the human body or to regulate the occurrence and progression of diseases. In this regard, there have been many investigations of cellular responses to the physical environment, such as electric field, fluid shear stress, and adhesion strength of the environment. In this dissertation, with respect to brain pathophysiology, we will investigate the cellular responses to a physical stimulus or environment and analyze them in both physical and biological meanings. First, we explored the effect of exogenous electrical stimulation (ES) on recovery from the Traumatic Brain Injury (TBI) in a rodent model. Our data showed that the ES at early phase of TBI increased the number of anti-inflammatory immune cells and neural stem cells at the injury site, which are important for recovery of the damaged brain. Secondly, we investigated the phenotypic transformation of microglia in response to shear flow using a microfluidic system to mimic the interstitial flow condition in the brain. Following the onset of the flow, microglia exhibited a transition from an oscillatory movement with a bipolar shape to a persistent migration with a unipolar shape. The observed dynamic transition was shown to strongly correlate with biological properties of the cells. Thirdly, we developed a strategy for isolating brain glial cells by modulating the surface wettability of cell culture substrate. On a hydrophobized surface, a mixed population of glial cells was successfully segregated into two distinct groups, namely single adherent microglia and spheroidal aggregation of astrocyte/oligodendrocyte based on their intrinsic adhesion characteristics. Overall, this study emphasizes the importance and applicability of engineering approaches to research in brain pathophysiology.