Age and Sex Differences in Hemodynamics in a Large Animal Model of Brain Trauma

Abstract

Traumatic brain injury (TBI) is a global health concern and is the leading cause of traumatic morbidity and mortality in children. Despite a lower overall mortality than in adult traumatic brain injury, the cost to society from the sequelae of pediatric traumatic brain injury is very high. Predictors of poor outcome after traumatic brain injury include altered systemic and cerebral physiology, including altered cerebral hemodynamics. Impaired cerebral hemodynamics, including cerebral blood flow and autoregulation following TBI may adversely impact poor outcome and may be age and or sex dependent. Yet, there is a paucity of information regarding changes in cerebral blood flow and cerebral autoregulation after pediatric TBI by age and sex. In this chapter, we first discuss clinical observations of pediatric TBI and how these can be used to better mimic TBI in a basic science large animal model of brain injury, the pig. Mechanistic explanations for age- and sex-dependent differences of TBI will focus on the spasmogen endothelin-1, glutamate, and the signaling system mitogen-activated protein kinase. Treatment strategies used for improvement of cerebral hemodynamics after TBI will consider the role of pressor choice in outcome. These data advocate for the consideration of development of sex-based therapies for treatment of hemodynamic sequelae of pediatric TBI.