Partial neuroprotection by nNOS inhibition during profound asphyxia in preterm fetal sheep

摘要: 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 a new, selective neuronal synthase (nNOS) inhibitor, JI-10 (0.022mg/kg bolus, n=8), given 30min 25min of complete umbilical cord occlusion was protective in preterm fetal sheep at 101-104day gestation (term 147days), compared saline (n=8). had no effect on blood pressure, heart rate, carotid femoral flow, total EEG power, nuchal activity, temperature or intracerebral oxygenation near-infrared spectroscopy after occlusion. later onset post-asphyxial seizures (p<0.05), attenuation subsequent progressive loss cytochrome oxidase (p<0.05). After 7days recovery, improved survival caudate nucleus but not putamen hippocampus, more CNPase positive oligodendrocytes periventricular white matter In conclusion, prophylactic nNOS inhibition profound asphyxia delayed seizures, slower decline partial gray protection, consistent protection function.