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

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 not been measured in the living neonatal brain yet.
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 DOPA decarboxylase (DDC), the ultimate enzyme in the synthesis of dopamine (DA), 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 two PET studies were performed under control conditions and during 2-hour asphyxia. Simultaneously, brain tissue pO₂ (LICOX pO₂ Monitor, GMS mbH, Kiel-Mielkendorf, Germany) was recorded, brain venous blood samples were obtained from sagittal sinus, and cerebral blood flow (CBF) was measured with col-ored microspheres. Cerebral metabolic rate of oxygen (CMRO2) was determined as the product of CBF and cerebral AVDO2. Asphyxia was induced by lowering the inspired fraction of oxygen from 0.35 to 0.12 and adding about 6 % CO₂ to the inspired gas, which resulted in moderate hypoxemia (39±6 mm Hg), hypercapnia (73±2 mm Hg) and a progredient combined respiratory/metabolic aci-dosis (p<0.01).
Asphyxia elicited an more than 3-fold increase of the CBF (p<0.01) so that CMRO2 remained un-changed throughout the asphyxial 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. However, striatal synthesis rate of FDA (fluoro-dopamine) from FDOPA (k3) was significantly increased (p<0.01).
This increase of the DDC activity due to moderately reduced brain tissue pO₂ at unchanged CMRO2 may contribute to the ...