Partial neuroprotection with low-dose infusion of the alpha2-adrenergic receptor agonist clonidine after severe hypoxia in preterm fetal sheep.
We have previously shown that brief alpha(2)-adrenergic receptor blockade increased neuronal injury after severe hypoxia in preterm fetal sheep. We now examine whether infusion of an alpha(2)-adrenergic receptor agonist, clonidine, is neuroprotective. Preterm fetal sheep (70% gestation) received either saline-vehicle or clonidine at either 10 microg/kg/h (low-dose) or 100 microg/kg/h (high-dose) from 15 min until 4 h after 25 min of umbilical cord occlusion. Both low- and high-dose clonidine infusions after sham-occlusion were associated with transient EEG suppression but no neuronal loss. Low-dose but not high-dose clonidine infusions after umbilical cord occlusion were associated with a significant overall increase in numbers of surviving neurons after three days' recovery. High-dose clonidine was associated with transient hyperglycemia and increased numbers of delayed electrographic seizures. These results provide further evidence that alpha(2)-adrenergic receptor activation shortly after perinatal hypoxia-ischemia can promote neural recovery, but highlight the complex dose-response of exogenous therapy.
Dean
Justin M
JM
Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
George
Sherly
S
Naylor
Andrew S
AS
Mallard
Carina
C
Gunn
Alistair J
AJ
Bennet
Laura
L
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003000:Clonidine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005260:Female; D000860:Hypoxia / Q000188:drug therapy* / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011247:Pregnancy; D047928:Premature Birth / Q000188:drug therapy*; D012756:Sheep; D013997:Time Factors; D014470:Umbilical Cord / Q000503:physiopathology
D000316:Adrenergic alpha-Agonists; D010751:Phosphopyruvate Hydratase; D003000:Clonidine