Increased platelet-activating factor-induced periventricular brain microvascular constriction associated with immaturity

1 Centre de Recherche de l'Hôpital Sainte-Justine, Department of Pediatrics and Pharmacology, Université de Montréal, Montréal, H3T 1C5; 2 Department of Pharmacology and Therapeutics, McGill University, Montréal, H3G 1Y6; and 3 Theratechnologies, Ville St-Laurent, Quebec, Canada, H4S 2A4 Oxidant stress contributes to the pathogenesis of hypoxic-ischemic encephalopathies. Platelet-activating factor (PAF) is generated during oxidant stress. We studied the vasomotor mode of actions of PAF on periventricular (PV) microvessels of fetal ( 75% of term), newborn (1-3 days), and adult pigs. PAF constricted PV microvessels from fetal (29.27 ± 2.6%) and newborn (22.14 ± 3.2%) pigs but was ineffective in adults ( newborn>adult profile. Thus the greater PAF-induced PV microvascular constriction in younger subjects seems attributable to greater PAF receptor density and mostly secondary to TXA 2 formation from endothelium. The resulting decrease in blood flow may contribute to the increased vulnerability of the PV brain regions to oxidant stress-induced injury in immature subjects. peroxidation; age dependence; thromboxane; ischemia