title: Effects of combination therapy using hypothermia and erythropoietin in a rat model of neonatal hypoxia-ischemia.
abstract: BACKGROUND
  Hypoxic-ischemic (HI) injury to the developing brain remains a major cause of morbidity. Hypothermia is effective but does not provide complete neuroprotection, prompting a search for adjunctive therapies. Erythropoietin (Epo) has been shown to be beneficial in several models of neonatal HI. This study examines combination hypothermia and treatment with erythropoietin in neonatal rat HI.
  
  
  METHODS
  Rats at postnatal day 7 were subjected to HI (Vannucci model) and randomized into four groups: no treatment, hypothermia alone, Epo alone, or hypothermia and Epo. Epo (1,000 U/kg) was administered in three doses: immediately following HI, and 24 h and 1 wk later. Hypothermia consisted of whole-body cooling for 8 h. At 2 and 6 wk following HI, sensorimotor function was assessed via cylinder-rearing test and brain damage by injury scoring. Sham-treated animals not subjected to HI were also studied.
  
  
  RESULTS
  Differences between experimental groups, except for Epo treatment on histopathological outcome in males, were not statistically significant, and combined therapy had no adverse effects.
  
  
  CONCLUSIONS
  No significant benefit was observed from treatment with either hypothermia or combination therapy. Future studies may require older animals, a wider range of functional assays, and postinsult assessment of injury severity to identify only moderately damaged animals for targeted therapy.
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Annie Y
authors.initials: AY
authors.lastname: Fang
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Gonzalez
authors.forename: R Ann
authors.initials: RA
authors.lastname: Sheldon
authors.forename: Donna M
authors.initials: DM
authors.lastname: Ferriero
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose; D001831:Body Temperature; D004921:Erythropoietin / Q000627:therapeutic use*; D006652:Histological Techniques; D007036:Hypothermia, Induced / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy*; D008297:Male; D051381:Rats
chemical_list: D001786:Blood Glucose; D004921:Erythropoietin