title: Gender associations with cerebrospinal fluid glutamate and lactate/pyruvate levels after severe traumatic brain injury.
abstract: OBJECTIVE
  Female sex hormones appear to be neuroprotective after traumatic brain injury by attenuating multiple mechanisms of secondary insult, including excitotoxicity and ischemia. The purpose of this study was to evaluate associations between gender and cerebrospinal fluid glutamate and lactate/pyruvate production and the role of hypothermia with gender in attenuating these markers.
  
  
  METHODS
  Prospectively collected data were analyzed for adult patients with severe traumatic brain injury. Gender comparisons for cerebrospinal fluid glutamate and lactate/pyruvate production were determined using ventricular samples obtained over the first 48 hrs postinjury.
  
  
  METHODS
  University-based level I trauma center.
  
  
  METHODS
  There were 123 patients, male n = 93 and female n = 30 (n = 686 cerebrospinal fluid samples), with severe traumatic brain injury (Glasgow Coma Scale score < or =8).
  
  
  METHODS
  A portion of these patients were part of a randomized controlled trial evaluating the effect of (48 hrs) therapeutic hypothermia after severe traumatic brain injury. The remainder received hypothermia (24 hrs) if they met clinical care criteria. Patients were cooled to 32-33 degrees C (within approximately 8 hrs) for either 24 or 48 hrs and then were rewarmed or remained normothermic.
  
  
  RESULTS
  Regression analyses using generalized estimating equations for repeated measures showed significant increases in cerebrospinal fluid glutamate production for males compared with females (p = .0023) and a significant interaction between glutamate concentration, gender, and time (p = .0035) by 24 hrs postinjury. Females had lower lactate/pyruvate ratios than males (p = .0006), and there was a significant interaction between lactate/pyruvate, gender, and time (p = .0045) throughout the first 48 hrs postinjury. Hypothermia attenuated glutamate levels, particularly for males, over the time course studied.
  
  
  CONCLUSIONS
  These data suggest significant gender differences with glutamate and lactate/pyruvate production after severe traumatic brain injury. Gender- and hormone-mediated differences in central nervous system pathophysiology should be considered with clinical trials in traumatic brain injury.
authors.affiliation: Safar Center for Resuscitation Research, Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wagner
authors.forename: Anthony
authors.initials: A
authors.lastname: Fabio
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.forename: Ronald
authors.initials: R
authors.lastname: Hirschberg
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Ross D
authors.initials: RD
authors.lastname: Zafonte
authors.forename: Donald W
authors.initials: DW
authors.lastname: Marion
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000628:therapy; D005260:Female; D015600:Glasgow Coma Scale; D018698:Glutamic Acid / Q000134:cerebrospinal fluid*; D006801:Humans; D007036:Hypothermia, Induced; D019344:Lactic Acid / Q000134:cerebrospinal fluid*; D008297:Male; D019289:Pyruvic Acid / Q000134:cerebrospinal fluid*; D016032:Randomized Controlled Trials as Topic; D012727:Sex Characteristics
chemical_list: D019344:Lactic Acid; D018698:Glutamic Acid; D019289:Pyruvic Acid