Perinatal hypoxic/ischemic encephalopathy: clinical challenge and experimental implications

Abstract

Perinatal asphyxia is an important cause of neonatal mortality and subsequent sequelae. Striatum, richly innervated by nigrostriatal dopaminergic projections, is susceptible to perinatal insults. Measuring the cerebral cortical oxygen pressure and striatal extracellular dopamine in the striatum in piglets under different kinds and degrees of hypoxia/ischemia insult, the changes of extracellular striatal dopamine were found to be more related to the changes in blood pressure than with cortical oxygen pressure. After asphyxia, cortical oxygen pressure was significantly higher in piglets breathing 100% O2 than in those breathing 21% O2. Two hours after reoxygenation, there was a secondary release of more dopamine in piglets ventilated with 100% O2 than in those with 21% O2. Although 100% FiO2 after asphyxia increases more cortical oxygenation, it also results in poorer recovery in dopamine metabolism and higher secondary release of striatal dopamine, which may exacerbate post-hypoxic cerebral injury. Striatal lesions may strongly be related with levels of extracellular dopamine during different degrees and kinds of insults. The study of the urine 1H-NMR spectra in newborns within six hours after birth demonstrated that the lactate/creatinine ratio in newborns with subsequent hypoxic-ischemic encephalopathy was significantly higher than in those with perinatal distress only and in normal newborns. The urine lactate/creatinine ratio in newborns with perinatal distress only was also significantly higher than that in normal newborns. The levels of urinary lactate/creatinine by 1H-NMR spectroscopy within six hours after birth correlates well with subsequent hypoxic-ischemic encephalopathy. The characteristics of urine 1H-NMR spectra can be sensitively and specifically used to identify early after birth for the asphyxiated newborns with potential subsequent hypoxic-ischemic encephalopathy.