Preservation of neural function in the perinate by high PGE(2) levels acting via EP2 receptors

Despite increasingly frequent and longer lasting hypoxic episodes during pr ogressive labor, the neonate is alert and vigorous at birth. We investigate d whether high levels of PGs during the perinatal period assist in preservi ng neural function after such "stressful" hypoxic events. Visual evoked pot entials (VEPs) and electroretinograms (ERGs) were recorded before and 45 mi n 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 epis ode, P2 and b-wave amplitudes were slightly decreased and latencies were de layed. These changes in the VEP and ERG returned to near normal by 120 min. Ibuprofen and diclofenac decreased brain and retinal PG levels and markedl y intensified 45 min after hypoxia-induced changes in VEP and ERG, but cere bral and retinal blood flows improved. Combined treatment with PG synthase inhibitor in combination with 16,16-dimethyl-PGE(2) (a PGE(2) analog), but not with PGI(2) and PGF(2 alpha) analogs, and in combination with the EP2 r eceptor agonist butaprost (but not EP1 or EP3 agonists), prevented ibuprofe n- and diclofenac-aggravated postasphyxia electrophysiological changes. In conclusion, high levels of PGE(2) in nervous tissue, via actions on EP2 rec eptors, seem to contribute to preservation of neural function in the perina te subjected to frequent hypoxic events.