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Increased platelet-activating factor-induced periventricular brain microvascular constriction associated with
Xin Hou1, Fernand Gobeil, Anne Marilise Marrache
1Centre de Recherche de l'Hôpital Sainte-Justine, Department of Pediatrics and Pharmacology, Université de Montréal, Montréal, H3T 1C5.
Summary
Platelet-activating factor (PAF) constricts brain blood vessels in newborns but not adults. This age-dependent effect, linked to PAF receptors and thromboxane A2, may explain why immature brains are vulnerable to hypoxic-ischemic injury.
Area of Science:
- Neuroscience
- Vascular Biology
- Perinatal Medicine
Background:
- Oxidant stress is implicated in hypoxic-ischemic encephalopathies.
- Platelet-activating factor (PAF) is produced during oxidant stress.
Purpose of the Study:
- To investigate the age-dependent effects of PAF on periventricular (PV) microvessels.
- To elucidate the mechanisms underlying PAF-induced vasoconstriction in immature subjects.
Main Methods:
- Studied vasomotor responses of PV microvessels from fetal, newborn, and adult pigs.
- Assessed specific [3H]PAF binding and PAF-induced inositol phosphate formation.
- Utilized thromboxane A2 (TXA2) synthase and receptor inhibitors, calcium channel blockers, and endothelium removal.
Main Results:
- PAF caused significant constriction in fetal and newborn PV microvessels, but not in adults.
- Higher specific [3H]PAF binding and inositol phosphate formation were observed in younger subjects.
- PAF-induced vasoconstriction was dependent on thromboxane A2 (TXA2) formation from the endothelium.
Conclusions:
- Greater PAF-induced PV microvascular constriction in immature pigs is attributed to increased PAF receptor density and TXA2 generation.
- Reduced blood flow due to PAF action may increase vulnerability to oxidant stress-induced brain injury in neonates.