Cellular mechanisms of traumatic brain injury.

Abstract

Mild traumatic brain injury (mTBI) is an acute injury with immediate and medium-term symptom presentation. However, our mechanistic understanding of mTBI and how mechanical loading of soft cellular tissues leads to injury is limited. The aim of this review is to introduce this interdisciplinary field to non-experts and provide an overview of our current understanding of how mechanical trauma contributes to cellular injury. Here, we compare the significance of various measures of mechanical loading including strain magnitude, strain rate, loading mode, and frequency, and their relative significance for cell and tissue injury in in vitro and ex vivo experimental models reported in the literature. Interestingly, while it is difficult to define a precise injury threshold value based on strain magnitude alone, cellular injury is commonly observed at strain rates of >0.1 s^-1, higher than rates observed in many normal cell functions (< 0.01 s^-1). We explore the role of the plasma membrane, cytoskeleton, and specialized structures in maintaining cell integrity during traumatic injury.