title: Sex and age differences in phenylephrine mechanisms and outcomes after piglet brain injury.
abstract: BackgroundTraumatic brain injury (TBI) is the leading cause of injury-related death in children, with boys and children under 4 years of age having particularly poor outcomes. Cerebral autoregulation is often impaired after TBI, contributing to poor outcome. In prior studies on newborn pigs, phenylephrine (Phe) preferentially protected cerebral autoregulation in female but not in male subjects 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.MethodsCerebral autoregulation, cerebrospinal fluid (CSF) extracellular signal-related kinase (ERK) and endothelin, and histopathology were determined after moderate fluid percussion brain injury (FPI) in male and female juvenile pigs after Phe.ResultsAutoregulation was more impaired in male than in female subjects. Phe protects autoregulation in both sexes after FPI, blocks ERK and endothelin, and decreases the number of necrotic neurons in male and female subjects after FPI.ConclusionsThese data indicate that Phe protects autoregulation and limits neuronal necrosis via blockage of ERK and endothelin after FPI in male and female subjects. Together with prior observations in newborn pigs where Phe protected autoregulation in female but not in male subjects, these data suggest that use of Phe to improve outcomes after TBI is both sex- and age-dependent.
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Victor
authors.initials: V
authors.lastname: Curvello
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Hugh
authors.initials: H
authors.lastname: Hekierski
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: John
authors.initials: J
authors.lastname: Riley
authors.affiliation: Department of Anesthesiology, University of Washington, Seattle, Washington.
authors.forename: Monica
authors.initials: M
authors.lastname: Vavilala
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania.|Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: William M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D002560:Cerebrovascular Circulation; D016232:Endothelins / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000134:cerebrospinal fluid / Q000378:metabolism; D005260:Female; D006706:Homeostasis; D007022:Hypotension; D008297:Male; D009336:Necrosis; D010656:Phenylephrine / Q000378:metabolism*; D010766:Phosphorylation; D012737:Sex Factors; D013552:Swine; D013696:Temperature; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D016232:Endothelins; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D048049:Extracellular Signal-Regulated MAP Kinases