Sex And Age Differences In Phenylephrine Mechanisms And Outcomes After Piglet Brain Injury

BACKGROUND: Traumatic brain injury (TBI) is the leading cause of injury related death in children, with boys and children under 4 having particularly poor outcomes. Cerebral autoregulation is often impaired after TBI, contributing to poor outcome. In prior studies of newborn pigs, phenylephrine (Phe) preferentially protected cerebral autoregulation in females but not males after TBI. We hypothesized that, in contrast to the newborn, Phe prevents impairment of autoregulation and tissue injury following TBI in both sexes of older pigs. METHODS: Cerebral autoregulation, CSF ERK and endothelin, and histopathology were determined after moderate fluid percussion brain injury (FPI) in male and female juvenile pigs after Phe. RESULTS: Autoregulation was more impaired in male subjects than females. Phe protects autoregulation in both sexes after FPI, blocked ERK and endothelin, and decreased the number of necrotic neurons in males and females after FPI. CONCLUSIONS: These data indicate that Phe protects autoregulation and limits neuronal necrosis via block of ERK and endothelin after FPI in maleas and females. Together with prior observations in newborn pigs where Phe protected autoregulation in female but not male subjects, these data suggest that use of Phe to improve outcome after TBI is both sex and age dependent.