The dopaminergic system is altered under neonatal asphyxia-studies with[¹⁸F]FDOPA.

There is evidence that the dopaminergic system is sensitive to asphyxia. However, the respective enzyme activities have not been measured in the living neonatal brain yet. In this study, FDOPA was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) and the relative changes of monoamine oxidase (MAO) and catechol-o-methyl-transferase (COMT) in the neonatal pig brain.
Two PET studies were performed under control conditions and under 2-hour asphyxia in each of 6 piglets and combined with measurements of cerebral blood flow (CBF) and volume (CBV). Plasma metabolites of FDOPA were also determined by HPLC.
As expected asphyxia elicited a 3-fold elevation of the CBF and increased the CBV by 40%. The blood-brain transfer of FDOPA, K₁, and the clearance rate constant from brain, k₂, were unchanged. However, the rate of [F-18]fluoro-dopamine synthesis, k₃, was increased in striatum from 0.038±0.016 min^-1 to 0.056±0.028 min^-1. Also, the rate of conversion of FDOPA to 3-O-methyl-FDOPA (OMFD) by COMT in plasma decreased during asphyxia from 0.0080±0.0015 min^-1 to 0.0046±0.0010 min^-1. Measurement of metabolites in tissue indicates that similar changes occurred also in the brain. Furthermore, the amount of FDOPAC as product of brain MAO activity was significantly decreased under asphyxia.
Increase of the extracellular level of dopamine is expected to be involved in severe disturbances of neuronal metabolism during asphyxia, e.g. by generating free radicals and quinones. In this study, evidence for an increase of the AADC activity and a decrease of MAO activity during asphyxia was obtained which may contribute to the increase of extracellular dopamine.