Publications by authors named "Gerd Vorwieger"

3 Publications

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Effect of moderate hypercapnic hypoxia on cerebral dopaminergic activity and brain O2 uptake in intrauterine growth-restricted newborn piglets.

Pediatr Res 2005 Mar 20;57(3):363-70. Epub 2004 Dec 20.

Institute of Pathophysiology and Pathobiochemistry, Universitätsklinikum Jena, Friedrich Schiller University, D-07740 Jena, Germany.

There is evidence that intrauterine growth restriction (IUGR) is associated with altered dopaminergic function in the immature brain. Compelling evidence exists that in the newborn brain, specific structures are especially vulnerable to O2 deprivation. The dopaminergic system is shown to be sensitive to O2 deprivation in the immature brain. However, the respective enzyme activities have not been measured in the living neonatal brain after IUGR under hypercapnic hypoxia (H/H). Therefore, 18F-labeled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography was used to estimate the aromatic amino acid decarboxylase activity of the brain of seven normal weight (body weight 2078 +/- 434 g) and seven IUGR newborn piglets (body weight 893 +/- 109 g). Two positron emission tomography scans were performed in each piglet. All animals underwent a period of normoxia and moderate H/H. Simultaneously, cerebral blood flow was measured with colored microspheres and cerebral metabolic rate of O2 was determined. In newborn normal-weight piglets, the rate constant for FDOPA decarboxylation was markedly increased in mesostriatal regions during H/H, whereas brain oxidative metabolism remained unaltered. In contrast, moderate H/H induced in IUGR piglets a marked reduction of clearance rates for FDOPA metabolites (p <0.05), which was accompanied by a tendency of lowering the rate constant for FDOPA conversion. Furthermore, IUGR piglets maintained cerebral O2 uptake in the early period of H/H, but during the late period of H/H, a significantly reduced cerebral metabolic rate of O2 occurred (p <0.05). Thus, IUGR is accompanied by a missing activation of dopaminergic activity and attenuated brain oxidative metabolism during moderate H/H. This may indicate endogenous brain protection against O2 deprivation.
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http://dx.doi.org/10.1203/01.PDR.0000150800.19956.F0DOI Listing
March 2005

The influx of neutral amino acids into the porcine brain during development: a positron emission tomography study.

Brain Res Dev Brain Res 2004 Sep;152(2):241-53

Institute of Interdisciplinary Isotope Research Leipzig, Permoserstrasse 15, D-04318 Leipzig, Germany.

Pigs of three different age groups (newborns, 1 week old, 6 weeks old) were used to study the transport of the large neutral amino acids 6-[18F]fluoro-L-DOPA ([18F]FDOPA) and 3-O-methyl-6-[18F]fluoro-L-DOPA ([18F]OMFD) across the blood-brain barrier (BBB) with positron emission tomography (PET). Compartmental modeling of PET data was used to calculate the blood-brain clearance (K1) and the rate constant for the brain-blood transfer (k2) of [18F]FDOPA and [18F]OMFD after i.v. injection. A 40-70% decrease of K1(OMFD), K1(FDOPA) and k2(OMFD) from newborns to juvenile pigs was found whereas k2(FDOPA) did not change. Generally, K1(OMFD) and k2(OMFD) are lower than K1(FDOPA) and k2(FDOPA) in all regions and age groups. The changes cannot be explained by differences in brain perfusion because the measured regional cerebral blood flow did not show major changes during the first 6 weeks after birth. In addition, alterations in plasma amino acids cannot account for the described transport changes. In newborn and juvenile pigs, HPLC measurements were performed. Despite significant changes of single amino acids (decrease: Met, Val, Leu; increase: Tyr), the sum of large neutral amino acids transported by LAT1 remained unchanged. Furthermore, treatment with a selective inhibitor of the LAT1 transporter (BCH) reduced the blood-brain transport of [18F]FDOPA and [18F]OMFD by 35% and 32%, respectively. Additional in-vitro studies using human LAT1 reveal a much lower affinity of FDOPA compared to OMFD or L-DOPA. The data indicate that the transport system(s) for neutral amino acids underlie(s) developmental changes after birth causing a decrease of the blood-brain barrier permeability for those amino acids during brain development. It is suggested that there is no tight coupling between brain amino acid supply and the demands of protein synthesis in the brain tissue.
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http://dx.doi.org/10.1016/j.devbrainres.2004.07.002DOI Listing
September 2004

Effect of hypoxia/hypercapnia on metabolism of 6-[(18)F]fluoro-L-DOPA in newborn piglets.

Brain Res 2002 Apr;934(1):23-33

Institute of Pathophysiology, Friedrich Schiller University, D-07740 Jena, Germany.

There is evidence that the dopaminergic system is sensitive to altered p(O(2)) in the immature brain. However, the respective enzyme activities have not been measured in the living neonatal brain together with brain oxidative metabolism. 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 fifteen newborn piglets (2-5 days old). Two PET scans were performed in each piglet. Eleven animals underwent a period of normoxia and moderate hypoxia/hypercapnia (H/H). The remaining four animals were used as an untreated control group. Simultaneously, the brain tissue p(O(2)) was recorded, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rate of oxygen (CMRO(2)) was determined. In addition, in four untreated and six H/H treated piglets the relative amounts of fluorodopamine and the respective metabolites were determined in brain tissue samples using HPLC analysis. H/H conditions were induced by lowering the inspired fraction of oxygen from 0.35 to 0.10 and adding CO(2) to the inspired gas resulting in an arterial p(CO(2)) between 74 and 79 mmHg. H/H elicited a more than 3-fold increase of the CBF (P<0.05) so that the CMRO(2) remained unchanged throughout the H/H period. Despite this, the brain tissue p(O(2)) was reduced from 19+/-4 to 6+/-3 mmHg (P<0.05). The permeability-surface area product of FDOPA (PS(FDOPA)) was unchanged. However, the transfer rate of FDOPA (k(3)(FDOPA)) of the nigrostriatal dopaminergic system and the relative amounts of fluorodopamine and the respective metabolites were significantly increased (P<0.05). It is suggested that H/H induces an increase of AADC activity. However, an H/H-induced CBF increase maintains bulk O(2) delivery and preserves CMRO(2).
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http://dx.doi.org/10.1016/s0006-8993(02)02315-6DOI Listing
April 2002