Brain- and heart-type fatty acid-binding proteins in the brain: tissue distribution and clinical utility.
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 microg/g wet weight in striatum tissue to 3.1 microg/g in frontal lobe. H-FABP was markedly higher, ranging from 16.2 microg/g wet weight in cerebellum tissue to 39.5 microg/g in pons. No B-FABP was detected in serum from healthy donors. H-FABP serum reference value was 6 microg/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 microg/L) in 17% of all samples (8 of 14 patients), and S100B was above its upper reference limit (0.3 microg/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.
Pelsers
Maurice M A L
MM
Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands. maurice.pelsers@gen.unimaas.nl
Hanhoff
Thorsten
T
Van der Voort
Daniëlle
D
Arts
Baer
B
Peters
Maarten
M
Ponds
Rudolf
R
Honig
Adriaan
A
Rudzinski
Wojtek
W
Spener
Friedrich
F
de Kruijk
Jelle R
JR
Twijnstra
Albert
A
Hermens
Wim T
WT
Menheere
Paul P C A
PP
Glatz
Jan F C
JF
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism*; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D004565:Electroconvulsive Therapy; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D005260:Female; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000097:blood; D012016:Reference Values; D009418:S100 Proteins / Q000097:blood; D018709:Statistics, Nonparametric; D014018:Tissue Distribution
D015415:Biomarkers; D002352:Carrier Proteins; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D009418:S100 Proteins; D010751:Phosphopyruvate Hydratase