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Proteomics and Protein Markers |
Departments of1
Molecular Genetics and 5
Biophysics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
2 Department of Biochemistry, University of Münster, Münster, Germany.
3 Department of Surgery, Medical Academy, Bialystok, Poland.
Departments of4
Psychiatry, 6
Neurology, and7
Clinical Chemistry, University Hospital Maastricht, Maastricht, The Netherlands.
aAddress correspondence to this author at: Department of Molecular Genetics, Maastricht, University, PO Box 616, 6200 MD Maastricht, The Netherlands. Fax 31-43-3884574; e-mail maurice.pelsers{at}gen.unimaas.nl.
Background: Detection of brain injury by serum markers is not a standard procedure in clinical practice, although several proteins, such as S100B, neuron-specific enolase (NSE), myelin basic protein, and glial fibrillary acidic protein, show promising results. We investigated the tissue distribution of brain- and heart-type fatty acid-binding proteins (B-FABP and H-FABP) in segments of the human brain and the potential of either protein to serve as plasma marker for diagnosis of brain injury.
Methods: B-FABP and H-FABP were measured immunochemically in autopsy samples of the brain (n = 6) and in serum samples from (a) patients with mild traumatic brain injury (MTBI; n = 130) and (b) depressed patients undergoing bilateral electroconvulsive therapy (ECT; n = 14). The protein markers S100B and NSE were measured for comparison. Reference values of B-FABP and H-FABP were established in healthy individuals (n = 92).
Results: The frontal, temporal, and occipital lobes, the striatum, the pons, and the cerebellum had different tissue concentrations of B-FABP and of H-FABP. B-FABP ranged from 0.8 µg/g wet weight in striatum tissue to 3.1 µg/g in frontal lobe. H-FABP was markedly higher, ranging from 16.2 µg/g wet weight in cerebellum tissue to 39.5 µg/g in pons. No B-FABP was detected in serum from healthy donors. H-FABP serum reference value was 6 µg/L. In the MTBI study, serum B-FABP was increased in 68% and H-FABP in 70% of patients compared with S100B (increased in 45%) and NSE (increased in 51% of patients). In ECT, serum B-FABP was increased in 6% of all samples (2 of 14 patients), whereas H-FABP was above its upper reference limit (6 µg/L) in 17% of all samples (8 of 14 patients), and S100B was above its upper reference limit (0.3 µg/L) in 0.4% of all samples.
Conclusions: B-FABP and H-FABP patterns differ among brain tissues, with the highest concentrations in the frontal lobe and pons, respectively. However, in each part of the brain, the H-FABP concentration was at least 10 times higher than that of B-FABP. Patient studies indicate that B-FABP and H-FABP are more sensitive markers for minor brain injury than the currently used markers S100B and NSE.
The following articles in journals at HighWire Press have cited this article:
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H. M.E. Azzazy, M. M.A.L. Pelsers, and R. H. Christenson Unbound Free Fatty Acids and Heart-Type Fatty Acid-Binding Protein: Diagnostic Assays and Clinical Applications Clin. Chem., January 1, 2006; 52(1): 19 - 29. [Abstract] [Full Text] [PDF] |
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L. Allard, P. R. Burkhard, P. Lescuyer, J. A. Burgess, N. Walter, D. F. Hochstrasser, and J.-C. Sanchez PARK7 and Nucleoside Diphosphate Kinase A as Plasma Markers for the Early Diagnosis of Stroke Clin. Chem., November 1, 2005; 51(11): 2043 - 2051. [Abstract] [Full Text] [PDF] |
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J. Ishii, Y. Ozaki, J. Lu, F. Kitagawa, T. Kuno, T. Nakano, Y. Nakamura, H. Naruse, Y. Mori, S. Matsui, et al. Prognostic Value of Serum Concentration of Heart-Type Fatty Acid-Binding Protein Relative to Cardiac Troponin T on Admission in the Early Hours of Acute Coronary Syndrome Clin. Chem., August 1, 2005; 51(8): 1397 - 1404. [Abstract] [Full Text] [PDF] |
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