Levels of proteins from the cerebrospinal fluid (CSF) such as S-100 and neuron-specific enolase (NSE) rise in brain parenchyma and are released in peripheral blood after a variety of cerebral lesions and injuries, including brain tumours, stroke, severe head injury, or multiple sclerosis. These proteins are generally considered markers of central nervous system damage. However, blood S-100 levels have been reported to increase in the absence of or prior to neuronal damage. Thus the early appearance of this protein in plasma may be the result of a disruption in the blood-brain barrier rather than of brain damage.

Because loss of blood-brain barrier integrity may precede neuronal damage in many conditions, early detection could potentially permit intervention to prevent irreversible brain damage. Currently, blood-brain barrier integrity can be assessed by contrast-enhanced computed tomography; a non-invasive alternative method would be useful. Two brain-specific proteins, S-100β and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100β levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100β is a marker of blood-brain barrier leakage rather than of neuronal damage. We measured both proteins in the plasma of patients undergoing iatrogenic blood-brain barrier disruption with mannitol, followed by methotrexate chemotherapy. Serum S-100β increased significantly after mannitol infusion (P < 0.05) while NSE did not. In similar patients who received methotrexate without mannitol, S-100β and NSE levels remained unchanged. This suggests that S-100β is an early marker of blood-brain barrier opening that is not necessarily related to neuronal damage.

erapy. Serum S-100β increased significantly after mannitol infusion (P < 0.05) while NSE did not. In similar patients who received methotrexate without mannitol, S-100β and NSE levels remained unchanged. This suggests that S-100β is an early marker of blood-brain barrier opening that is not necessarily related to neuronal damage.