A Mechanistic End-to-End Concussion Model That Translates Head Kinematics to Neurologic Injury

Abstract

Past concussion studies have focused on understanding the injury processes occurring on discrete length scales (e.g., tissue-level stresses and strains, cell-level stresses and strains, or injury-induced cellular pathology). A comprehensive approach that connects all length scales and relates measurable macroscopic parameters to neurological outcomes is the first step toward rationally unraveling the complexity of this multi-scale system, for better guidance of future research. This paper describes the development of the first quantitative end-to-end (E2E) multi-scale model that links gross head motion to neurological injury by integrating fundamental elements of tissue and cellular mechanical response with axonal dysfunction. The model quantifies axonal stretch (i.e., tension) injury in the corpus callosum, with axonal functionality parameterized in terms of axonal signaling. An internal injury correlate is obtained by calculating a neurological injury measure (the average reduction in the axonal signal amplitude) over the corpus callosum. By using a neurologically based quantity rather than externally measured head kinematics, the E2E model is able to unify concussion data across a range of exposure conditions and species with greater sensitivity and specificity than correlates based on external measures. In addition, this model quantitatively links injury of the corpus callosum to observed specific neurobehavioral outcomes that reflect clinical measures of mild traumatic brain injury. This comprehensive modeling framework provides a basis for the systematic improvement and expansion of this mechanistic-based understanding, including widening the range of neurological injury estimation, improving concussion risk correlates, guiding the design of protective equipment, and setting safety standards.

Normal Alert Consciousness - A Central Executive Model of Hippocampal Function

“…Concussions result from blunt force to the skull generating torsional forces that damage the brain. Models of the impact calculate that the greatest torsional forces appear in the interior of the skull, including the corpus callosum and nearby structures such as the hippocampus [308][309][310]. These forces stretch nerve fibers in the region; evidence suggests this damage may result in necrosis a few days after the initial injury.…”

Introductory Chapter: A Brief Survey of the Functional Roles of the Hippocampus

“…During concussions, blunt force to the skull typically generates torsional forces that damage the brain. The greatest torsional forces appear in the interior of the skull, including the corpus callosum and nearby structures such as the hippocampus [73][74][75]. These forces stretch nerve fibers in the region, resulting in necrosis.…”

Diffuse Axonal Injury: A Devastating Pathology

“…Forces of greater magnitude striking the head almost immediately disconnect axons within the site of impact. Secondary axon disconnections also develop resulting in severe brain injury [8,9]. Human physiological symptoms as a result of trauma also set in, such as swelling and degeneration of nerves.…”