title: Combination treatment with 17β-estradiol and therapeutic hypothermia for transient global cerebral ischemia in rats.
abstract: OBJECTIVE
  Therapeutic hypothermia is now regarded as the only effective treatment of global ischemic injury after cardiac arrest. Numerous studies of the neuroprotective effects of 17β-estradiol have yielded conflicting results depending on administration route and dose. Herein, we investigated the neuroprotective effect of postischemic 17β-estradiol administration combined with therapeutic hypothermia.
  
  
  METHODS
  Twenty-one rats were randomly divided into 4 groups: control (group I), therapeutic hypothermia (group II), 17β-estradiol treatment (group III), and therapeutic hypothermia combined with 17β-estradiol treatment (group IV). One rat was assigned to a sham operation group. With the exception of the sham-operated rat, all animals underwent transient global cerebral ischemia for 20 minutes by the 4-vessel occlusion method. Hypothermia was maintained at 33°C for 2 hours in groups II and IV, and 17β-estradiol (10 μg/kg) was intraperitoneally administered to rats in groups III and IV. Neurologic deficit scores and hippocampal cornu ammonis 1 neuronal injury were assessed 72 hours postischemia.
  
  
  RESULTS
  The neurologic deficit score was not significantly different among the groups. The percentage of normal neurons in the hippocampal cornu ammonis 1 was 7.32% ± 0.88% in group I, 53.65% ± 2.52% in group II, 51.6% ± 3.44% in group III, and 79.79% ± 1.6% in group IV. The neuroprotective effect in the combined treatment group was markedly greater than in the single treatment groups, which suggests that hypothermia and 17β-estradiol work synergistically to exert neuroprotection.
  
  
  CONCLUSIONS
  Postischemic administration of low-dose 17β-estradiol appears to be neuroprotective after transient global ischemia, and its effect is potentiated by therapeutic hypothermia.
authors.affiliation: Department of Emergency Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Joo Suk
authors.initials: JS
authors.lastname: Oh
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Kim
authors.forename: Hang Joo
authors.initials: HJ
authors.lastname: Cho
authors.forename: Yeon Young
authors.initials: YY
authors.lastname: Kyong
authors.forename: Young Min
authors.initials: YM
authors.lastname: Oh
authors.forename: Se Min
authors.initials: SM
authors.lastname: Choi
authors.forename: Kyoung Ho
authors.initials: KH
authors.lastname: Choi
authors.forename: Kyu Nam
authors.initials: KN
authors.lastname: Park
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D004958:Estradiol / Q000494:pharmacology*; D007036:Hypothermia, Induced; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000628:therapy*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric
chemical_list: D018696:Neuroprotective Agents; D004958:Estradiol