Relation between brain tissue pO₂ and dopamine synthesis of basal ganglia - A ¹⁸FDOPA-PET study in newborn piglets

Abstract

Perinatal hypoxic-ischemic cerebral injury is a major determinant of neurologic morbidity and mortality in the neonatal period and later in childhood. There is evidence that the dopaminergic system is sensitive to oxygen deprivation. However, the respective enzyme activities have yet not been measured in the living neonatal brain. In this study, we have used ¹⁸F-labelled 6-fluoro- L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography (PET) to estimate the activity of the aromatic amino acid decarboxylase (AADC), the ultimate enzyme in the synthesis of dopamine, in the brain of newborn piglets under normoxic and moderate asphyxial conditions. The study was performed on 8 newborn piglets (2–5 days old). In each piglet PET studies were performed under control conditions and during 2-hour asphyxia. Simultaneously, brain tissue pO₂ was recorded, cerebral blood flow (CBF) was measured with colored microspheres and cerebral metabolic rate of oxygen (CMRO₂) was determined. Asphyxia was induced by lowering the inspired fraction of oxygen from 0.35 to 0.10 and adding about 6% CO₂ to the inspired gas.

Asphyxia elicited a more than 3-fold increase of the CBF (p < 0.01) so that CMRO₂ remained unchanged throughout the as phyxial period. Despite this, brain tissue pO₂ was reduced from 19 ± 4 mm Hg to 6 ± 3 mm Hg ( p < 0.01). Blood-brain transfer of FDOPA as well as permeability-surface area product (PS) from striatum were unchanged. Striatal synthesis rate of fluoro-dopamine from FDOPA (k₃) was, however, significantly increased (p < 0.01).

This increase of the AADC activity is associated with reduced brain tissue pO₂. Asphyxia-induced CBF increase impedes an alteration of brain oxidative metabolism.