title: How long is too long for cerebral cooling after ischemia in fetal sheep?
abstract: Therapeutic hypothermia can partially reduce long-term death and disability in neonates after hypoxic-ischemic encephalopathy. The aim of this study was to determine whether prolonging the duration of cooling from 3 days to 5 days could further improve outcomes of cerebral ischemia in near-term fetal sheep. Fetal sheep (0.85 gestation) received 30 minutes bilateral carotid artery occlusion followed by 3 days of normothermia (n = 8), 3 days of hypothermia (n = 8), or 5 days of hypothermia (n=8) started 3 hours after ischemia. Sham controls received sham ischemia followed by normothermia (n = 8). Cerebral ischemia was associated with profound loss of electroencephalography power and spectral edge, with greater and more rapid recovery in both hypothermia groups (P<0.05). Ischemia was associated with severe loss of neurons in the cortex, hippocampus and thalamus (P < 0.05), with a significant improvement in both hypothermia groups. However, the ischemia-3-day hypothermia group showed greater neuronal survival in the cortex and dentate gyrus compared with ischemia-5-day hypothermia (P < 0.05). Ischemia was associated with induction of iba1-positive microglia, which was attenuated in both hypothermia groups (P < 0.05). Extending the duration of delayed therapeutic hypothermia from 3 to 5 days did not improve outcomes after severe ischemia, and was associated with reduced neuronal survival in some regions.
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Joanne O
authors.initials: JO
authors.lastname: Davidson
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Guido
authors.initials: G
authors.lastname: Wassink
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Yuill
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Zhang
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
authors.affiliation: Department of Physiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D005333:Fetus / Q000378:metabolism / Q000473:pathology; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012756:Sheep; D013997:Time Factors