gardiquimod and Asphyxia-Neonatorum

Activation of Toll-like receptors (TLRs) after hypoxic-ischemic brain injury can exacerbate injury but also alleviate cell loss, as recently demonstrated with the TLR7 agonist Gardiquimod (GDQ). However, TLR agonists also modulate vascular function and neuronal excitability. Thus, we examined the effects of TLR7 activation with GDQ on cardiovascular function and seizures after asphyxia in preterm fetal sheep at 0.7 gestation (104 days, term ∼147 days). Fetuses received sham asphyxia or asphyxia induced by umbilical cord occlusion for 25 min or asphyxia followed by a continuous intracerebroventricular infusion of 3.34 mg of GDQ from 1 to 4 h after asphyxia. Fetuses were monitored continuously for 72 h postasphyxia. GDQ treatment was associated with sustained, moderate hypertension for 72 h (

Topics: Aminoquinolines; Animals; Animals, Newborn; Asphyxia Neonatorum; Blood Pressure; Brain Waves; Disease Models, Animal; Gestational Age; Heart Rate; Hypertension; Imidazoles; Neuroprotective Agents; Premature Birth; Risk Assessment; Seizures; Sheep, Domestic; Signal Transduction; Tachycardia; Time Factors; Toll-Like Receptor 7