Peripheral markers of brain damage and blood-brain barrier dysfunction

Issue title: Molecular Markers of Brain Damage – Current State and Future Perspectives

Article type: Research Article

Authors: Marchi, Nicola | Rasmussen, Peter | Kapural, Miranda | Fazio, Vince | Kight, Kelly | Mayberg, Marc R. | Kanner, Andrew | Ayumar, Barbara | Albensi, Ben | Cavaglia, Marco | Janigro, Damir^;

Affiliations: Cerebrovascular Research Center, Department of Neurological Surgery Cleveland Clinic Foundation, Cleveland, OH 44195, USA | Cerebrovascular Research Center, Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA

Note: [] Corresponding author: Damir Janigro, Ph.D., Director, Cerebrovascular Research, Cleveland Clinic Foundation NB20, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel.: +1 216 445 0561; Fax: +1 216 445 1466; E-mail: janigrd@ccf.org

Abstract: Purpose: Occurrence of brain damage is frequently associated with abnormal blood-brain barrier (BBB) function. Two brain-specific proteins, S100β and neuron-specific enolase (NSE) are released systemically in a variety of neurological diseases, but S100β levels sometimes rise in the absence of neuronal damage, suggesting that S100β 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 S100β increased significantly after mannitol infusion (p<0.05) while NSE did not. Furthermore, in a model of intracerebral hemorrhage, S100β increases in CSF did not lead to serum changes at a time when the BBB was intact. Modeling of S100β release from the CNS suggested that low (<0.34 ng/ml) serum levels of S100β are consistent with BBB opening without CNS damage, while larger increases imply synthesis and release from presumable damaged glia. Conclusions: Thus, S100β in serum is an early marker of BBB openings that may precede neuronal damage and may influence therapeutic strategies. Secondary, massive elevations in S100β 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.

Keywords: S100β, cerebrovascular disease, diagnostics, endothelium, magnetic resonance imaging, neurological disorders, cerebral ischemia

Journal: Restorative Neurology and Neuroscience, vol. 21, no. 3-4, pp. 109-121, 2003