Cleveland Clinic Researchers Identify Sensitive Marker of Blood-Brain Barrier Failure That Does Not Necessarily Indicate Brain Damage
Neurosciences 07/31/2007
S100b is a protein that is constitutively expressed by brain astrocytes and physiologically does not appear in minimal concentration in the systemic circulation. In the past, elevated S100blevels in cerebrospinal fluid and serum were believed to correlate with the extent of brain damage. Recent evidence from the laboratory of Dmir Janigro, PhD, Staff Director, Cerebrovascular Research, Cleveland Clinic Lerner Research Institute, demonstrates that S100b is a sensitive marker of blood-brain barrier failure that does not necessarily indicate brain damage.
With this in mind, Dr. Janigro and his collaborators, Nicola Marchi, PhD, and Andrew Kanner, MD, prospectively studied serum S100b levels in patients undergoing hyperosmotic blood-brain barrier (BBB) disruption for intra-arterial chemotherapy for primary central nervous system lymphoma. In addition, serum S100b samples were measured in patients with a variety of primary or metastatic brain lesions at the time of magnetic resonance imaging (MRI) neuroimaging was obtained. This was intended to provide both information on the time course of S100b appearance in the peripheral blood circulation, and to allow the correlation of findings on MRI. These studies indicated that S100b directly correlated with the degree of clinical and radiological signs of BBB disruption in patients who were enrolled in the hyperosmotic study.
Furthermore, in patients with neoplastic brain lesions, Gadolinium enhancement on MRI correlated with elevated S100b levels versus non-enhancing scans. Primary brain tumors or CNS metastases presented with significantly elevated serum S100b. Details of these studies will be published in Restorative Neurology and Neuroscience, and in Cancer in the upcoming months.
The same researchers have also identified a protein marker that could detect disease and determine when the body may be receptive to medication.
"We are excited by this discovery and are ready to explore it potential," said Dr. Janigro. "This protein marker, dubbed transthyretin monomer (TTR), could deliver potentially life-saving medications when the body's natural defense mechanisms are temporarily breached."
The defense mechanisms to which Dr. Janigro refers protect the brain from foreign substances by creating barriers between the blood and the brain, as well as between the blood and cerebrospinal fluid (CSF).
"This finding may have significant implications in the development of simple diagnostic tools for conditions affecting the central nervous system," Dr. Janigro said. "Additionally, discovery of this marker may help us manage or diagnose disorders such as stroke, brain tumors, inflammations of the nervous system and other cerebrovascular disorders."
The findings of Dr. Janigro and Dr. Marchi, who identified TTR, were published in the March 1st, 2003, edition of The Journal of Neuroscience.
For more information, please call Damir Janigro, PhD at 216.445.0561.
Relationship between radiological findings, brain lesions and serum S100β.
Plot of S100β values in patients undergoing contrast-enhanced MRi scans. Note that negative findings correlate well with normal S100β (dashed-line).
MRI scans from selected patients: B1, meningioma with extensive peritumoral edema; B2, meningeoma post-resection, negative MRI; B3, breast cancer metastasis.
S100β levels in patients affected by a variety of tumor pathologies. Allmets = all metastatic brain tumors.