Serum S100beta: a noninvasive marker of blood-brain barrier function and brain lesions.
BACKGROUND
S100beta protein is expressed constitutively by brain astrocytes. Elevated S100beta levels in cerebrospinal fluid and serum reported after head trauma, subarachnoid hemorrhage, and stroke were correlated with the extent of brain damage. Because elevated serum S100beta also was shown to indicate blood-brain barrier (BBB) dysfunction in the absence of apparent brain injury, it remains unclear whether elevation of serum levels of S100beta reflect BBB dysfunction, parenchymal damage, or both.


METHODS
The authors conducted a prospective study of serum S100beta levels in six patients who underwent hyperosmotic BBB disruption (BBBD) with intraarterial chemotherapy for primary central nervous system lymphoma. In addition, 53 serum S100beta samples were measured in 51 patients who had a variety of primary or metastatic brain lesions at the time of neuroimaging.


RESULTS
S100beta was correlated directly with the degree of clinical and radiologic signs of BBBD in patients who were enrolled in the hyperosmotic study. In patients with neoplastic brain lesions, gadolinium enhancement on a magnetic resonance image was correlated with elevated S100beta levels (n = 45 patients; 0.16 +/- 0.1 microg/L; mean +/- standard error of the mean) versus nonenhancing scans (n = 8 patients; 0.069 +/- 0.04 microg/L). Primary brain tumors (n = 8 patients; 0.12 +/- 0.08) or central nervous system metastases also presented with elevated serum S100beta levels (n = 27 patients; 0.14 +/- 0.34). Tumor volume was correlated with serum S100beta levels only in patients with vestibular schwannoma (n = 6 patients; 0.13 +/- 0.10 microg/L) but not in patients with other brain lesions.


CONCLUSIONS
S100beta was correlated directly with the extent and temporal sequence of hyperosmotic BBBD, further suggesting that S100beta is a marker of BBB function. Elevated S100beta levels may indicate the presence of radiologically detectable BBB leakage. Larger prospective studies may better determine the true specificity of S100beta as a marker for BBB function and as an early detection or follow-up marker of brain tumors.
Kanner
Andrew A
AA
Brain Tumor Institute, The Cleveland Clinic, Ohio 44195, USA.
Marchi
Nicola
N
Fazio
Vincent
V
Mayberg
Marc R
MR
Koltz
Michael T
MT
Siomin
Vitaly
V
Stevens
Glen H J
GH
Masaryk
Thomas
T
Aumayr
Barbara
B
Ayumar
Barbara
B
Vogelbaum
Michael A
MA
Barnett
Gene H
GH
Janigro
Damir
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D001812:Blood-Brain Barrier / Q000502:physiology*; D001932:Brain Neoplasms / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D011446:Prospective Studies; 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