Partial neuroprotection with low dose infusion of the 2-adrenergic receptor agonist clonidine after severe hypoxia in preterm fetal sheep.

Abstract

We have previously shown that brief a2-adrenergic receptor blockade increased neuronal injury after severe hypoxia in preterm fetal sheep. We now examine whether infusion of an a2-adrenergic receptor agonist, clonidine, is neuroprotective. Preterm fetal sheep (70% gestation) received either saline-vehicle or clonidine at either 10 mg/kg/h (low-dose) or 100 mg/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 a2-adrenergic receptor activation shortly after perinatal hypoxia–ischemia can promote neural recovery, but highlight the complex dose–response of exogenous therapy. 2008 Elsevier Ltd. All rights