Neuroendocrine dysfunction following traumatic brain injury (TBI) has been described extensively. However, few studies are longitudinal and most lack subtle radiological, clinical, and repetitive endocrine assessment in the acute phase. Accordingly, we prospectively assessed neuroendocrine function in 71 patients after TBI. Injury was documented by a computed tomography (CT). During the first week, critical clinical data (Glasgow Coma Score, APACHE score), treatment variables such as duration of analgosedation for mechanical ventilation, were related to basal pituitary function. More than 2 years later, a subgroup of patients was re-evaluated using dynamic testing with ACTH and GHRH-arginine tests. The Pearson's correlation analysis and Mann-Whitney rank sum test for group differences were used for statistical analysis. None of the CT findings predicted neuroendocrine dysfunction following TBI. The adaptive response to critical illness with significantly elevated cortisol levels on admission and decreased levels thereafter in patients ventilated for more than 24 h ( p < 0.05) was attenuated following severe TBI ( p < 0.05). However, the coincidence of low serum cortisol and increased urinary excretion of glucocorticoid metabolites in about 80% of patients challenges the relevance of basal hormone measurements. In ventilated patients, total T3 and free T4 were decreased ( p < 0.05), TSH was low on day 3 ( p < 0.05), and a gonadotropic insufficiency was present ( p < 0.05). The thyrotropic and gonadotropic system recovered completely within the follow-up period. With regard to the somatotropic system, neither brain injury severity nor mechanical ventilation was associated with an insufficiency during the acute phase post-injury. However, initially low GH levels predicted a persistent deficiency (r = 0.731, p < 0.001). We conclude that both severe TBI and prolonged mechanical ventilation result in hormonal disturbances early after injury, suggesting a pathophysiological response to brain injury and subsequent intensive care treatment rather than morphological damage.

S100B is a 21-kDa protein that is produced and secreted by astrocytes and widely used as a marker of brain injury in clinical and experimental studies. The majority of these studies are based on measurements in blood serum, assuming an associated increase in cerebrospinal fluid and a rupture of the blood–brain barrier (BBB). Moreover, extracerebral sources of S100B are often underestimated. Herein, we will review these interpretations and discuss the routes by which S100B, produced by astrocytes, reaches the circulatory system. We discuss the concept of S100B as an alarmin and its dual activity as an inflammatory and neurotrophic molecule. Furthermore, we emphasize the lack of data supporting the idea that S100B acts as a marker of BBB rupture, and the need to include the glymphatic system in the interpretations of serum changes of S100B. The review is also dedicated to valorizing extracerebral sources of S100B, particularly adipocytes. Furthermore, S100B per se may have direct and indirect modulating roles in brain barriers: on the tight junctions that regulate paracellular transport; on the expression of its receptor, RAGE, which is involved in transcellular protein transport; and on aquaporin-4, a key protein in the glymphatic system that is responsible for the clearance of extracellular proteins from the central nervous system. We hope that the data on S100B, discussed here, will be useful and that it will translate into further health benefits in medical practice.

Following brain injury, S100B is released from damaged astrocytes but also yields repair mechanisms. We measured S100B in the cerebrospinal fluid (CSF) and serum (Cobas e411 electrochemiluminescence assay, Roche) longitudinally in a large cohort of patients treated with a ventricular drainage following traumatic brain injury (TBI) or subarachnoid hemorrhage (SAH). Statistical analysis was performed with SPSS software applying the Mann-Whitney rank sum test or chi-test where appropriate. S100B in CSF and serum was significantly increased following TBI (n=71) and SAH (n=185) for at least one week following injury. High S100B levels in CSF and serum were inconsistent associated with outcome. The passage of S100B from CSF to blood (100∗serumS100B/CSFS100B) was significantly decreased although the albumin quotient suggested an “open” blood-CSF barrier. Events possibly interfering with the BBB did not affect the S100B passage (P=.591). In conclusion, we could not confirm S100B measurements to reliably predict outcome, and a compromised blood-CSF barrier did not affect the passage of S100B from CSF to serum.