Peripheral markers of brain damage and blood-brain barrier dysfunction.
OBJECTIVE
Occurrence of brain damage is frequently associated with abnormal blood-brain barrier (BBB) function. Two brain-specific proteins, S100beta and neuron-specific enolase (NSE) are released systemically in a variety of neurological diseases, but S100beta levels sometimes rise in the absence of neuronal damage, suggesting that S100beta is a marker of BBB rather than neuronal damage.


METHODS
We measured both proteins in the serum of patients undergoing iatrogenic BBB disruption with intrarterial mannitol, followed by chemotherapy.


RESULTS
Serum S100beta increased significantly after mannitol infusion (p<0.05) while NSE did not. Furthermore, in a model of intracerebral hemorrhage, S100beta increases in CSF did not lead to serum changes at a time when the BBB was intact. Modeling of S100beta release from the CNS suggested that low (<0.34 ng/ml) serum levels of S100beta are consistent with BBB opening without CNS damage, while larger increases imply synthesis and release from presumable damaged glia.


CONCLUSIONS
Thus, S100beta in serum is an early marker of BBB openings that may precede neuronal damage and may influence therapeutic strategies. Secondary, massive elevations in S100beta are indicators of prior brain damage and bear clinical significance as predictors of poor outcome or diagnostic means to differentiate extensive damage from minor, transient impairment.
Marchi
Nicola
N
Cerebrovascular Research Center, Department of Neurological Surgery Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Rasmussen
Peter
P
Kapural
Miranda
M
Fazio
Vince
V
Kight
Kelly
K
Mayberg
Marc R
MR
Kanner
Andrew
A
Ayumar
Barbara
B
Albensi
Ben
B
Cavaglia
Marco
M
Janigro
Damir
D
D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D001927:Brain Diseases / Q000097:blood / Q000473:pathology; D006801:Humans; D002534:Hypoxia, Brain / Q000097:blood* / Q000473:pathology; D009414:Nerve Growth Factors / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood
D015415:Biomarkers; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D010751:Phosphopyruvate Hydratase