Traumatic Brain Injury: Linking Macro- to Micro-Biomechanics
Traumatic Brain Injury (TBI) is unique from any other neurological disorder or disease in that it is induced by a physical event. Supra-threshold traumatic loading may cause structural damage ranging from overt tissue disruption to extremely subtle, subcellular damage. Such physical damage may directly precipitate secondary pathophysiology in addition to providing the context in which negative intracellular cascades unfold. This underscores the need to accurately represent tissue- and cellular-level injury biomechanics to fully describe clinical TBI as well as to develop and validate experimental models.
Our Approach: To understand Mechanisms and Consequences Of Neural Cellular “Pathological Mechanosensation” in TBI
We determine injury tolerance criteria based on acute biophysical disruptions and evolving neurodegeneration
We apply a multi-level approach including in vitro (2-D/3-D cell culture) and in vivo (rodent and porcine) models
Goal: understand cell/tissue biomechanics to establish links between physical and physiological consequences of TBI
3-D In Vitro Model of TBI
Movies
Volumetric reconstruction of a 3-D neuronal-astrocytic co-culture
Volumetric reconstruction of a 3-D neuronal-astrocytic co-culture after injury
Caption: Cell death and network degeneration following high strain rate deformation.
In Vivo Model of TBI
Accordingly, a major objective of the Cullen Lab is to link macro- to micro- brain injury biomechanics with acute cellular damage and evolving neuropathology across various experimental models of TBI. We have developed a unique experimental framework to establish the relationships between defined cell- and tissue-level biomechanical inputs and acute structural/biophysical alterations that may be responsible for neural cell death or persistent dysfunction. Attention to the injury biomechanics is important for establishing links between the physical and physiological consequences of TBI, thus facilitating the development of targeted medical therapeutics to address the predominantly afflicted cell populations based on the mechanisms of injury.
