In Vitro Remodeling of Extracellular Matrix Following Mild Traumatic Brain Injury

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Virginia Tech


Every year millions of individuals suffer from traumatic brain injury (TBI) leading to permanent disabilities and even death. Mild TBI (mTBI) is the most common form of TBI comprising about 80-90% of all occurrences. Following a CNS insult like an mTBI, astrocytes can undergo activation resulting in the transformation into reactive astrocytes (RAs). RAs also play an important role in brain remodeling following an mTBI. Research on the mechanical complexity of the brain has important implications for understanding brain function and dysfunction, as well as for the development of new diagnostic and therapeutic tools for neurological disorders. This study aimed to develop and utilize an emph{in vitro} mTBI platform to investigate the intricate mechanical interplay between the extracellular matrix (ECM) and astrocytes following a simulated mTBI. Cellular mechanisms underlying mTBI and the contribution of mechanical forces that result in prolonged brain damage are yet to be comprehensively understood. Successfully devised mechanical characterization techniques for tissue-engineered models were developed utilizing atomic force microscopy and rheology. Astrocyte exposure to high-rate overpressure revealed altered mechanical properties of the surrounding matrix and decreased expression of laminin and collagen IV, which are critical for brain function and may contribute to pathologies associated with mTBI. The developed platform and methods provide new insights into the mechanistic complexity underlying ECM-astrocyte interactions following an mTBI.



Traumatic Brain Injury, Extracellular Matrix Remodelling, Reactive Astrocytes