Fig. 2. In vitro models of CNS trauma.
Mechanical models of CNS injury aim to recreate the biomechanical parameters that underlie specific injury subtypes to recapitulate secondary injury mechanisms and the injury microenvironment. a. Impact-based models utilize a weight-drop or ballistic pendulum mechanism to induce blunt tissue damage or to recreate collisional impact, respectively. b. Stretch-induced injury models deform surrogate tissue or cells cultured on a flexible substrate, such as polydimethylsiloxane (PDMS), using compressed gas or by lowering the substrate onto an indenter platform. Biaxial and uniaxial strain can be applied based on the type of apparatus and setup employed. Microfabricated devices are used to compartmentalize and isolate axonal projections in microgrooves for investigation of axonal stretch injury. c. Transection models induce axotomy using laser or vacuum in investigations of axonal degeneration and regeneration. Microfabricated platforms with microgrooves are used in transection models to separate somatodendritic and axonal compartments to isolate axotomy and observe injury-induced alterations in synapse remodeling and synaptic function. d. Aspects of secondary injury pathogenesis are modeled in isolation to control for confounding pathology, especially in investigations of mechanism of action. 3D co-culture models have been developed using collagen or alginate to encapsulate primary neural cells in studies of perilesional tissue architecture alterations following injury. 2D monolayer cultures are used to investigate post-injury cell-cell interactions and injury-induced biochemical changes in neurons and glial cells. Modified culture conditions, such as oxygen/glucose deprivation, and treatments with chemicals are used to mimic the injury microenvironment and to control for confounding factors. Part of Figure 2b is adapted from [26] and is licensed under a Creative Commons Attribution 4.0 International License, which allows use, sharing, adaptation, distribution and reproduction. Copy of license: http://creativecommons.org/licenses/by/4.0/.