title: Hemodynamic and metabolic correlates of perinatal white matter injury severity.
abstract: OBJECTIVE
  Although the spectrum of perinatal white matter injury (WMI) in preterm infants is shifting from cystic encephalomalacia to milder forms of WMI, the factors that contribute to this changing spectrum are unclear. We hypothesized that the variability in WMI quantified by immunohistochemical markers of inflammation could be correlated with the severity of impaired blood oxygen, glucose and lactate.
  
  
  METHODS
  We employed a preterm fetal sheep model of in utero moderate hypoxemia and global severe but not complete cerebral ischemia that reproduces the spectrum of human WMI. Since there is small but measurable residual brain blood flow during occlusion, we sought to determine if the metabolic state of the residual arterial blood was associated with severity of WMI. Near the conclusion of hypoxia-ischemia, we recorded cephalic arterial blood pressure, blood oxygen, glucose and lactate levels. To define the spectrum of WMI, an ordinal WMI rating scale was compared against an unbiased quantitative image analysis protocol that provided continuous histo-pathological outcome measures for astrogliosis and microgliosis derived from the entire white matter.
  
  
  RESULTS
  A spectrum of WMI was observed that ranged from diffuse non-necrotic lesions to more severe injury that comprised discrete foci of microscopic or macroscopic necrosis. Residual arterial pressure, oxygen content and blood glucose displayed a significant inverse association with WMI and lactate concentrations were directly related. Elevated glucose levels were the most significantly associated with less severe WMI.
  
  
  CONCLUSIONS
  Our results suggest that under conditions of hypoxemia and severe cephalic hypotension, WMI severity measured using unbiased immunohistochemical measurements correlated with several physiologic parameters, including glucose, which may be a useful marker of fetal response to hypoxia or provide protection against energy failure and more severe WMI.
authors.affiliation: Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Art
authors.initials: A
authors.lastname: Riddle
authors.affiliation: Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Maire
authors.affiliation: Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Victor
authors.initials: V
authors.lastname: Cai
authors.affiliation: Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Thuan
authors.initials: T
authors.lastname: Nguyen
authors.affiliation: Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Xi
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hansen
authors.affiliation: Department of Pathology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Marjorie R
authors.initials: MR
authors.lastname: Grafe
authors.affiliation: Department of Obstetrics and Gynecology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: A Roger
authors.initials: AR
authors.lastname: Hohimer
authors.affiliation: Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, United States of America ; Department of Neurology, Oregon Health & Science University, Portland, Oregon, United States of America.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Back
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001774:Blood Chemical Analysis; D001786:Blood Glucose; D001794:Blood Pressure; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology*; D005311:Fetal Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics; D007150:Immunohistochemistry; D019344:Lactic Acid / Q000097:blood; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D010100:Oxygen / Q000097:blood; D047928:Premature Birth; D012756:Sheep
chemical_list: D001786:Blood Glucose; D019344:Lactic Acid; D010100:Oxygen