Preservation of neural function in the perinate by high PGE2 levels acting via EP2 receptors

Despite increasingly frequent and longer lasting hypoxic episodes during progressive labor, the neonate is alert and vigorous at birth. We investigated whether high levels of PGs during the perinatal period assist in preserving neural function after such “stressful” hypoxic events. Visual evoked potentials (VEPs) and electroretinograms (ERGs) were recorded before and 45 min after mild moderate asphyxic hypoxia (two 4-min asphyxic-hypoxic periods induced by interrupting ventilation at 8-min intervals) in newborn piglets <12 h old treated or not treated with inhibitors of PG synthase (ibuprofen or diclofenac) with or without PG analogs. At 45 min after the hypoxic episode, P2 and b-wave amplitudes were slightly decreased and latencies were delayed. These changes in the VEP and ERG returned to near normal by 120 min. Ibuprofen and diclofenac decreased brain and retinal PG levels and markedly intensified 45 min after hypoxia-induced changes in VEP and ERG, but cerebral and retinal blood flows improved. Combined treatment with PG synthase inhibitor in combination with 16,16-dimethyl-PGE2 (a PGE2 analog), but not with PGI2 and PGF2α analogs, and in combination with the EP2 receptor agonist butaprost (but not EP1 or EP3 agonists), prevented ibuprofen- and diclofenac-aggravated postasphyxia electrophysiological changes. In conclusion, high levels of PGE2 in nervous tissue, via actions on EP2 receptors, seem to contribute to preservation of neural function in the perinate subjected to frequent hypoxic events.