Sex and Age Differences in Epinephrine Mechanisms and Outcomes after Brain Injury.

Abstract

Traumatic brain injury (TBI) is the leading cause of injury-related death in children, with boys and children <4 years of age having particularly poor outcomes. Cerebral autoregulation is often impaired after TBI, contributing to poor outcome. Cerebral perfusion pressure can be normalized by use of vasoactive agents. The c-Jun-terminal kinase (JNK) isoform of mitogen activated protein kinase (MAPK) produces hemodynamic impairment after TBI, but less is known about its role in histopathology. We investigated whether epinephrine (EPI), age, and sex dependently protected cerebral autoregulation and limited histopathology after TBI, and sought to determine the role of JNK in that outcome. Lateral fluid percussion injury (FPI) was produced in anesthetized pigs. Pial artery reactivity was measured via a closed cranial window. Phosphorylated JNK MAPK was quantified by enzyme-linked immunosorbent assay (ELISA). Results show that EPI preserves autoregulation, prevents histopathology, and blocks phosphorylated JNK upregulation in newborn males and females and juvenile females but not juvenile males after TBI. These data indicate that EPI preserves cerebral autoregulation and limits histopathology after TBI through blockade of JNK in an age- and sex-dependent manner.