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Exposure to chronic hypoxia during gestation predisposes infants to neonatal pulmonary hypertension, but the underlying mechanisms remain unclear. Here, we test the hypothesis that moderate continuous hypoxia during gestation causes changes in the rho-kinase pathway that persist in the newborn period, altering vessel tone and responsiveness. Lambs kept at(More)
BACKGROUND AND PURPOSE The fetus is well known to be able to survive prolonged exposure to asphyxia with minimal injury compared with older animals. We and others have observed a rapid suppression of EEG intensity with the onset of asphyxia, suggesting active inhibition that may be a major neuroprotective adaptation to asphyxia. Adenosine is a key regulator(More)
A significant proportion of temporal lobe epilepsy (TLE), a common, intractable brain disorder, arises in children with febrile status epilepticus (FSE). Preventative therapy development is hampered by our inability to identify early the FSE individuals who will develop TLE. In a naturalistic rat model of FSE, we used high-magnetic-field MRI and long-term(More)
The reaction of nitrite with deoxyhemoglobin results in the production of nitric oxide and methemoglobin, a reaction recently proposed as an important oxygen-sensitive source of vasoactive nitric oxide during hypoxic and anoxic stress, with several animal studies suggesting that nitrite may have therapeutic potential. Accumulation of toxic levels of(More)
This paper reviews the scientific evidence for the safety of carbon monoxide (CO) and nitric oxide (NO) inhalation to measure pulmonary diffusing capacity (DL(CO) and DL(NO)) in pregnant women and their fetuses. In eight earlier studies, 650 pregnant women had DL(CO) measurements performed at various times during pregnancy, with a minimum of two to four(More)
Vitamin D deficiency has been associated with pregnancy complications such as preeclampsia, gestational diabetes, and recurrent miscarriage. Therefore, we hypothesized differences in vitamin D status between healthy [Sprague-Dawley (SD) and Lewis (LW)] and complicated [Brown Norway (BN)] rat pregnancies. In SD, LW, and BN rats, we analyzed the maternal(More)
Preterm brain injury is partly associated with hypoxia-ischemia starting before birth. Excessive nitric oxide production during HI may cause nitrosative stress, leading to cell membrane and mitochondrial damage. We therefore tested the hypothesis that therapy with a new, selective neuronal nitric oxide synthase (nNOS) inhibitor, JI-10 (0.022mg/kg bolus,(More)
Recent evidence from humans and rats indicates that nitrite is a vasodilator under hypoxic conditions by reacting with metal-containing proteins to produce nitric oxide (NO). We tested the hypothesis that near-physiological concentrations of nitrite would produce vasodilation in a hypoxia- and concentration-dependent manner in the hind limb of sheep.(More)
Cerebral vessels in the premature newborn brain are well supplied with adrenergic nerves, stemming from the superior cervical ganglia (SCG), but their role in regulation of blood flow remains uncertain. To test this function twelve premature or two-week-old lambs were instrumented with laser Doppler flow probes in the parietal cortices to measure changes in(More)
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