Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs.
There is evidence that the dopaminergic system is sensitive to traumatic brain injury (TBI). However, the age-dependency of this sensitivity has not been studied together with brain oxidative metabolism. We postulate that the acute effects of severe TBI on brain dopamine turnover are age-dependent. Therefore 18F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with Positron-Emission-Tomography (PET) was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) in the brain of 11 newborn piglets (7-10 days old) and nine juvenile pigs (6-7 weeks old). Six newborn and five juvenile animals were subjected to a severe fluid-percussion (FP) induced TBI. The remaining animals were used as sham operated untreated control groups. Simultaneously, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rates of oxygen and glucose were determined. At 1 h after FP-TBI, [18F]FDOPA was infused and PET scanning was performed for 2 h. At 2 h after FP-TBI administration, a second series of measurements of physiological values including CBF and brain oxidative metabolism data had been obtained. Severe FP-TBI elicited a marked increase in the rate constant for fluorodopamine production (k3FDOPA) in all brain regions of newborn piglets studied by between 97% (mesencephalon) and 143% (frontal cortex) (p < 0.05). In contrast, brain hemodynamics and cerebral oxidative metabolism remained unaltered after TBI. Furthermore, the permeability-surface area product of FDOPA (PSFDOPA) was unchanged. In addition, regional blood flow differences between corresponding ipsi- and contralateral brain regions did not occur after TBI. Thus, it is suggested that severe FP-TBI induces an upregulation of AADC activity of newborn piglets that is not related to alterations in brain oxidative metabolism.
Department of Neurosurgery, Friedrich Schiller University Jena, Germany.
Bernd
B
Walter
Peter
P
Brust
Frank
F
Füchtner
Marco
M
Müller
Rainer
R
Hinz
Hiroto
H
Kuwabara
Harald
H
Fritz
Ulrich
U
Zwiener
Reinhard
R
Bauer
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000254:growth & development* / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005947:Glucose / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D049268:Positron-Emission Tomography; D034421:Sus scrofa; D015854:Up-Regulation / Q000502:physiology
C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D005947:Glucose; D004298:Dopamine