Integrated Model of Traumatic Brain Injury Multiple Morbidity

Clinical and pathological study of traumatic brain injury (TBI) has revealed that this significant event frequently impacts the quality of life by inducing lingering multiple disabilities of cognitive, anxiety, balance, and motor functions. Studies of impact acceleration closed-head TBI utilizing instrumented head models with force sensors revealed that peak shearing forces occurred in the rostral brainstem due to the disparity of movement of the forebrain compared to the tethered brainstem. The resident tissue in the brainstem region subjected to the peak shearing force includes the cells and projection fibers of the nucleus locus coeruleus, a primary noradrenergic nucleus of the central nervous system. Preclinical studies have confirmed that closed-head TBI produced diffuse injuries of the cells and projection fibers of the locus coeruleus component of the central noradrenergic system. Due to the multiple input/output connectivity of the locus coeruleus with multiple brain regions, this type of injury can result in disabilities in cognition, anxiety, balance, and motor systems: together, these considerations can be collected into an integrative systems model of multiple morbidity following injury of the central noradrenergic system. To better understand the relationship between LC injury and multiple disabilities, a brief synopsis of the types of influence LC-NA projections have on the excitability of neurons in some representative regions pertinent to cognition, anxiety, balance, motor systems, motor cortex, and motor neurons is briefly discussed.