Perinatal asphyxia has been reported to occur in between 1 in 50 and 1 in 500 live births and remains a major cause of childhood neurodevelopmental handicap. At the time of cerebral imaging or postmortem examination, a common finding in infants with perinatal asphxyia is periventricular white matter (PVWM) destruction. We hypothesize that the sensitivity of the PVWM to asphyxial insult may be attributed to the failure of the neonatal cerebrovasculature to provide adequate cerebral blood flow (CBF) to this region and that this failure of CBF to the PVWM may in part be secondary to the failure of the PVWM to produce increased prostanoid compounds in response to insult. We also hypothesize that both the relative preservation of CBF to the cortical and central gray matter and the increase in regional prostaglandin concentrations found there in animals exposed to a model for perinatal asphyxia may be inhibited by the cyclo- oxygenase inhibitor, indomethacin. Utilizing a model for perinatal asphyxia in the newborn beagle pup, we will employ both serial radioactive microsphere and 14C iodoantipyrine autoradiography methods in a model for perinatal asphyxia to examine the hypothesis that there is relative preservation of gray matter CBF compared to flow to the PVWM in this model. In addition, animals expose to this model will be pretreated with either saline or indomethacin to examine the hypothesis that prostaglandins may in part control local CBF. A parallel series of experiments will be performed in which gray and white matter prostaglandin levels will be measured to document the effect of indomethacin and asphyxia on these brain compartments. Finally, neuropathologic studies will be performed to document the neuropathological changes produced by this insult.
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| Ment, L R; Stewart, W B; Petroff, O A et al. (1989) Beagle puppy model of perinatal asphyxia: blockade of excitatory neurotransmitters. Pediatr Neurol 5:281-6 |
| Ment, L R; Stewart, W B; Petroff, O A et al. (1989) Thromboxane synthesis inhibitor in a beagle pup model of perinatal asphyxia. Stroke 20:809-14 |
| Ment, L R; Ehrenkranz, R A; Duncan, C C (1988) Intraventricular hemorrhage of the preterm neonate: prevention studies. Semin Perinatol 12:359-72 |
| Ment, L R; Stewart, W B; Gore, J C et al. (1988) Beagle puppy model of perinatal asphyxia: alterations in cerebral blood flow and metabolism. Pediatr Neurol 4:98-104 |
| Ment, L R (1988) Intraventricular hemorrhage of the preterm neonate: prevention studies. Mead Johnson Symp Perinat Dev Med :19-26 |
| Ment, L R (1988) Perinatal asphyxia: clinical and experimental studies. Mead Johnson Symp Perinat Dev Med :27-35 |
