title: Hypothermia and erythropoietin for neuroprotection after neonatal brain damage.
abstract: BACKGROUND
  Both hypothermia and erythropoietin (EPO) are reported to have neuroprotective effects after perinatal hypoxia-ischemia (HI). We investigated a possible additive effect of the use of a combination of hypothermia-EPO in a rat model of neonatal HI.
  
  
  METHODS
  At postnatal day 7, rats were subjected to HI and then randomized to 3 h of hypothermia, EPO, or both. Sensorimotor function was assessed by the cylinder-rearing test (CRT) at 2 and 5 wk after HI. Brain lesion volume and white matter loss were determined by hematoxylin-eosin and luxol fast blue staining, respectively.
  
  
  RESULTS
  Multivariable analysis using general linear modeling showed that hypothermia, EPO, and the interaction hypothermia × gender were determinants of sensorimotor function, both at 2 and 5 wk after HI. Neuroprotective effects of hypothermia at 5 wk were more pronounced in females, showing 52% improvement in the CRT. Maximal improvement in males was 26% after combined treatment with hypothermia and EPO. Histological outcome was improved by hypothermia only with no additional effect of EPO or gender.
  
  
  CONCLUSIONS
  Hypothermia after HI improved sensorimotor function in females more than in males. There was a borderline additive effect of EPO when combined with hypothermia. Histology of brain lesion volume and white matter damage was improved only by hypothermia.
authors.affiliation: Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Fan
authors.forename: Frank
authors.initials: F
authors.lastname: van Bel
authors.forename: Michael A
authors.initials: MA
authors.lastname: van der Kooij
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: Floris
authors.initials: F
authors.lastname: Groenendaal
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose; D001831:Body Temperature; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006652:Histological Techniques; D007036:Hypothermia, Induced / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D016014:Linear Models; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D018696:Neuroprotective Agents; D004921:Erythropoietin