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Occurrence of brain damage is frequently associated with abnormal blood-brain barrier (BBB) function. Two brainspecific proteins, S100β• and neuron-specific enolase (NSE) are released systemically in a variety of neurological disease, but S100β levels sometimes rise in the absence of neuronal damage, suggesting that S100β is a marker of BBB rather than neuronal damage. We measured both proteins in the serum of patients undergoing iatrogenic BBB disruption with intrarterial mannitol, followed by chemotherapy. Serum S100β increased significantly after mannitol infusion (p< 0. 05) while NSE did not. Furthermore, in a model of intracerebral hemorrhage, S100βincreases 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 …