Dynamics of S100B Release into Serum and Cerebrospinal Fluid Following Acute Brain Injury

High S100B serum levels are considered to reflect brain injury severity. However, the dynamics of S100B passage from the cerebral compartment into the blood remain unclear. We examined the temporal profile of S100B release into the cerebrospinal fluid (CS

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Abstract  High S100B serum levels are considered to reflect brain injury severity. However, the dynamics of S100B passage from the cerebral compartment into the blood remain unclear. We examined the temporal profile of S100B release into the cerebrospinal fluid (CSF) and blood in acute brain injury. In patients treated with ventricular drainage (subarachnoid hemorrhage, SAH, n = 23; traumatic brain injury, TBI, n = 19), we measured S100B levels in the serum and CSF. The Glasgow Coma Score (GCS) was assessed daily. Statistical analysis was performed by the Mann–Whitney rank sum test for group differences and by the Pearson correlation. In normal controls (n = 6), S100B levels in the serum (0.05 ± 0.01 µg/L) comprised around 10% of the CSF concentration (0.66 ± 0.08 µg/L). Following brain injury, S100B levels were significantly increased in the serum (p < 0.05 in SAH day 2–5, TBI day 1–8) and excessively increased in the CSF (p < 0.05 in SAH and TBI day 1–10). For the individual patient, there was no consistent correlation between S100B levels in serum or CSF and GCS. We therefore calculated the ratio of S100B serum/ CSF. Following brain injury, the S100B passage from the CSF to the blood was significantly impaired. Further, higher ratios were correlated with better neurological function (p = 0.002). Because stimulated active S100B release may serve as a repair mechanism, a higher S100B serum/CSF ratio may contribute to neurological recovery. Keywords  Biomarker • outcome • neurotrophic factor • traumatic brain injury

A. Kleindienst (*), S. Meissner, I.Y. Eyupoglu, C. Schmidt, and M. Buchfelder Department of Neurosurgery, Friedrich-Alexander-University Erlangen-Nuremberg, Schwabachanlage 6, Erlangen D-91054, Germany e-mail: [email protected] H. Parsch University Erlangen-Nuremberg, Central Laboratory, Erlangen, Germany

Introduction The early assessment of injury severity and consequent prognosis are major concerns for physicians treating patients suffering from brain injury, and there is a desire for a reliable indicator to accurately determine the extent of the brain damage. The measurement of putative biochemical markers, such as the S100B protein, has been proposed in this role. Over the past decade, numerous studies have reported a positive correlation between S100B serum levels and poor outcome following brain injury (10). However, some evidence raises doubts regarding whether the serum measurement of S100B is a valid biomarker of brain damage (7). The neurotrophic protein S100B belongs to a multigenic family of low molecular weight (9–13 kD) calcium-binding S100 proteins (5). S100B is most abundant in glial cells of the central nervous system, predominately in astrocytes (3). Experimental findings demonstrate that S100B is secreted from astroglia within a few minutes after receptor activation, and release may last up to 10 h (2, 12). Although injury-induced S100B release continues to increase up to 48 h in cell cultures (11, 13), S100B serum levels in patients are highest directly after the in