Dynamic change of serum protein S100b and its clinical significance in patients with traumatic brain injury

Withgradualclarificationofmolecularconstitutionandbiologicalactivities,studiesinrecentdecadeshaveprovedthatproteinS100b,asaneurobiochemicalmarker,hasbecomeaspecificproteinthatcanbestreflectbraininjuryseverityand prognosis.1Inourstudy,wehavediscussedthe associationofserumS100bproteinwithtraumaticbrain injuryaswellasitsclinicalsignificancethrough observingdynamicchangesofserumS100bproteinby ELISA.METHODS Materials Atotalof102casesofbraininjuryadmittedinto traumaticsurgerydepartmentofourhos…     

Predictive value of S-100B protein and neuron specific-enolase as markers of traumatic brain damage in clinical use

Objective: S-100B and NSE proteins are considered to be neurobiochemical markers for the brain damage. The aim of this study was to consider the diagnostic and prognostic validity of the initial serum levels of S-100B and NSE in clinical use.

Methods: Forty-five patients with traumatic brain injury were included in this prospective study. Neurologic examination and CCT-scan were performed. S-100B and NSE were analysed. Patients were divided in two groups depending on the severity of injury.

Results: The results showed a significant difference between the S-100B serum concentration and the two groups—minor head injuries and severe head injuries. A statistically significant correlation was observed between an increase of S-100B and NSE serum values and a cerebral pathological finding in CT scans.

Conclusion: The clear correlation between S-100B and NSE serum concentrations and CCT findings does not validate both markers as an independent predictor of diagnosis and prognosis of brain injury.     

Protein S-100B as a serum marker of brain damage in severe head injury: preliminary results

The objective of our study was to investigate S-100B protein as a serum marker of brain cell damage after severe head injury. Eighty-three patients with severe head injury (Glasgow Coma Scale ≤8) were included in this prospective study. Venous blood samples for S-100B protein were taken after admission and every 24 h for a maximum of 10 consecutive days. Outcome was assessed at 6 months using the Glasgow Outcome Scale. In this study, we analysed the preliminary results from the outcomes of 25 patients at 6 months. Levels of S-100B were significantly higher in patients with unfavourable outcome compared to those with favourable outcome. In patients with favourable outcome, slightly increased initial levels of S-100B returned to normal within 3 to 4 days. In patients with unfavourable outcome, initial levels were markedly increased, with a tendency to decrease from day 1 to day 6. After day 6, there was a secondary increase in serum S-100B, indicating secondary brain cell damage. Our preliminary results suggest that serum S-100B protein might be a promising biochemical marker which may provide additional information on the extent of primary injury to the brain and the prediction of outcome after severe head injury. Received: 10 June 1999 / Accepted: 3 August 1999     

Circulating S100B is increased after bilateral femur fracture without brain injury in the rat

Background. S100B is an acknowledged marker of brain damage.However, trauma without brain damage also causes an increasein S100B. S100B concentrations are highest in multiple traumapatients with long bone fractures. Clinically, extensive longbone fractures are associated with haemorrhagic shock and haemorrhagicshock per se is associated with increased S100B. The aim ofour experimental study was to verify the S100B increase in longbone fracture without haemorrhagic shock. Methods and results. Bilateral femur fracture was carried outin 10 anaesthetized rats. Blood samples were drawn for immuno-luminometricalS100B measurement 5, 15, 30, 120, and 240 min after fracture.Mean arterial pressure (MAP), heart rate, and body temperaturewere monitored continuously. S100B increased after bilateralfemur fracture and reached a peak 30–120 min after fracture(P<0.001). MAP remained at a level which is not associatedwith shock in rats. Heart rate and body temperature remainedunchanged. Autopsy verified open bilateral femur fracture surroundedonly by small zones of clotted blood. Conclusions. S100B is increased in bilateral femur fracturewithout haemorrhagic shock in rats. This finding suggests thatbone marrow is a potential extracerebral source of S100B. Br J Anaesth 2003; 91: 595–7     

Delayed rises in serum S100B levels and adverse neurological outcome in infants and children undergoing cardiopulmonary bypass

BACKGROUND: The protein S100B is a marker of brain injury. Early after cardiopulmonary bypass (CPB), serum S100B levels are artefactually high. We investigated whether delayed (48 h) rise in S100B levels may have a role in detecting brain injury after CPB. METHODS: Data from 43 children were analysed in this study. Samples were collected at preincision and 30 min, 24 and 48 h postbypass and then analysed by using a commercially available radioimmunoassay (Sangtec100). Charts were reviewed at 3-5 months for evidence of neurological injury. RESULTS: S100B levels were high preoperatively in neonates and universally high immediately postbypass. In 36 children, samples were available for all time points. Compared with preoperative levels, rises occurred at both 24 and 48 h in three patients, only at 24 h in four patients and only at 48 h in three patients. Two patients had evidence of neurological injury. A rise at 48 h was associated with neurological injury (odds ratio 33.9, P < 0.03, 95% CI 1.39-827). There was no association between neurological injury and S100B levels at 24 h. Both the patients with neurological injury had rises at 48 h that were significantly higher than patients with rises at 48 h without injury. CONCLUSIONS: The results of this study suggest that monitoring S100B levels in the late postoperative period may still have a role in detecting neurological injury after cardiac surgery in children. Consistent with previous observations, S100B is high preoperatively in neonates and early postbypass in all patients.     

S-100B Protein Serum Levels After Controlled Cortical Impact Injury in the Rat

S-100B is described to provide information about the severity of brain damage in man. Estimation of serum markers appears to be an easy method of obtaining information regarding severity and outcome after head injury. However less is known about the post traumatic time course of this protein in the serum. The aim of this study was to provide further information about the posttraumatic enzymekinetik. 65 male Wistar rats were subjected to severe cortical impact injury (100 PSI, 2 mm deformation). Blood samples were drawn directly after trauma, then after 1 h, 6 h, 12 h, 24 h, and 48 h. In sham operated animals blood samples were drawn directly after craniotomy, then after 6 h and after 48 h. Also compared were S-100B serum levels at different severities in 20 rats (45 PSI, 75 PSI; 2 mm deformity) after controlled cortical impact to sham operated animals. S-100B serum levels were estimated with a commercially available enzyme immuno-assay (DAKO). The mean serum level in the sham group was 0.38 microg/l. Serum levels at 100 PSI differed statistically significantly directly after trauma up to 24 h. The 48 h S-100B levels showed no significant difference in the sham group. Serum levels at different severities differed significantly from the sham group, but did not differ concerning level of severity. The controlled cortical impact model is able to produce a raised serum level of the S-100B protein for 24 hours. Different trauma severities were not reflected.     

硫酸镁对急性重型颅脑损伤患者血清S-100B蛋白浓度的影响

目的通过动态观察硫酸镁对急性重型颅脑损伤患者血清S-100B蛋白浓度的影响，进一步探讨硫酸镁在急性重型颅脑损伤治疗中的作用。方法将120例急性重型颅脑损伤患者随机分为硫酸镁组和常规组。硫酸镁组在常规治疗的基础上，予25％硫酸镁8ml用生理盐水稀释至100ml匀速静脉推注，时间为15分钟。然后将25％硫酸镁30ml加入5％葡萄糖500ml中用24小时缓慢静脉滴注，输液泵控制输液速度，连续用7天。所有患者于入院6小时内，入院后第2、3、4、5、6天动态检测血清S-100B蛋白浓度。3个月后对患者进行GOS评估。结果硫酸镁组和常规组血清S-100B蛋白浓度明显高于正常对照组（P〈0，05）；硫酸镁组血清S-100B蛋白浓度明显低于常规组（P〈0．05）；硫酸镁能够改善急性熏型颅脑损伤患者的预后。结论急性重型颅脑损伤患者血清S-100B蛋白浓度明显升高，早期应用硫酸镁能显著降低患者血清S-100B蛋白浓度，保护神经功能．改善预后。     

SIOOB protein and its clinical effect on craniocerebra injury

Objective： To explore the role of S100B protein in the early diagnosis, treatment, and prognosis judgement of craniocerebral injury.
Methods： In this study, we reviewed the domestic and foreign research reports about the relationship between S100B protein and craniocerebral injury.
Results： The concentration of S100B protein had a different increase based on the degree of injury in early stage after craniocerebral injury, and the increasing degree of S100B protein showed a positive correlation with the grading of pathogenetic condition and prognosis of craniocerebral injury.
Conclusions： S100B protein may be taken as a specific index of early diagnosis, grading of pathogenetic condition, and prognosis judgement after craniocerebral injury. To grasp and regulate the mechanism of neurotoxicity and to elucidate the therapeutic effect of S100B protein will be a research direction in clinical treatment of craniocerebral injury.     

Correlation of Computed Tomography Findings and Serum Brain Damage Markers Following Severe Head Injury

Summary  The objective of our study was to investigate the association between the initial levels of serum S-100B protein and neuron specific enolase and the severitiy of radiologically visible brain damage and outcome after severe head injury.  Admission computed tomography (CT) scans of forty-four patients with severe head injury were analysed. Initial levels of S-100B protein and neuron specific enolase were compared between the different outcome groups at 6 month, the different categories of the Marshall classification, the presence of traumatic subarachnoid haemorrhage, the type of haematoma and the volume of contusion.  Serum S-100B was significantly higher in patients with unfavourable outcome (1.1 μg/1 versus 0.3 μg/1, p<0.005, Mann-Whitney U test). In diffuse injury, unfavourable outcome significantly increased with higher Marshall grades (p<0.05). There was a significant correlation between the four grades of diffuse injury and initial serum S-100B protein (r=0.48, p<0.001). Patients with focal mass lesions and a favourable outcome after 6 month had significantly lower S-100B values than those who had an unfavourable outcome (0.51 μg/l versus 1.3 μg/1, p<0.05). A significant correlation was demonstrated between the volume of contusion visible on CT scans and serum S-100B (r=0.58, p<0.001).  In our study, initial serum S-100B protein was a powerful predictor of outcome even within the same category of radiologically visible brain damage. Serum S-100B protein may provide independent information about the severity of primary brain damage after head injury.     

The prognostic value of serum S-100B protein in spontaneous subarachnoid haemorrhage

Summary Background. Despite the major progress in neurophysiological monitoring, there are still difficulties in the early identification and quantification of cerebral damage after a stroke. In this prospective study we examined the associations between serum S-100B protein, a serum marker of brain injury, and initial neurological-neuroimaging severity, secondary deterioration, external ventricular drainage (EVD: therapeutic intervention) and outcome in patients with subarachnoid haemorrhage (SAH). Method. We recorded all pertinent clinical data of 52 patients with SAH and measured S-100B serum levels on admission and every 24 h for a maximum of 9 consecutive days. Mann–Whitney U-test and Kruskal Wallis analysis were employed to assess the association of S-100B levels with all variables of interest. Log-rank test was used to evaluate survival and Cox’s proportional hazard regression analysis to define the significant predictors of survival rate. Findings. Admission S-100B was statistically significantly associated with initial neurological status, neuroimaging severity, and one-year outcome (p = 0.0002, 0.001, and 0.017, Kruskal Wallis analysis). Admission S-100B above 0.3 μg/L predicted unfavourable outcome (p < 0.0001, log rank test) and constituted an independent predictor of short-term survival (p = 0.035 Cox’s proportional hazard regression analysis) with a hazard ratio of 2.2 (95% C.I.: 1.06–4.6) indicating a more than doubling of death probability. Secondary neurological deterioration associated with S-100B increase (p < 0.0001) and external ventricular drainage (EVD) with S-100B reduction (p = 0.003, Wilcoxon signed rank test). Conclusions. Serum S-100B protein seems to be a useful biochemical indicator of neurological – neuroimaging severity, secondary deterioration, EVD (therapeutic intervention), and outcome in patients with SAH.     

Serum S-100B and cleaved-tau are poor predictors of long-term outcome after mild traumatic brain injury

Primary objective: To determine the relationship of serum S-100B and C-tau levels to long-term outcome after mild traumatic brain injury (mild TBI). Research design: A prospective study of 35 mild TBI subjects presenting to the emergency department. Methods and procedures: Six hour serum S-100B and C-tau levels compared to 3-month Rivermead Post Concussion Questionnaire (RPCQ) scores and post-concussive syndrome (PCS). Main outcomes and results: The linear correlation between marker levels and RPCQ scores was weak (S-100B: r = 0.071, C-tau: r = -0.21). There was no statistically significant correlation between marker levels and 3-month PCS (S-100B: AUC = 0.589, 95%CI. 038, 0.80; C-tau: AUC = 0.634, 95%CI 0.43, 0.84). The sensitivity of these markers ranged from 43.8-56.3% and the specificity from 35.7-71.4%. Conclusions: Initial serum S-100B and C-tau levels appear to be poor predictors of 3-month outcome after mild TBI.     

Release of S100B during coronary artery bypass grafting is reduced by off-pump surgery

Background. S100B, a plasma marker of brain injury, was compared after coronary artery bypass grafting with and without cardiopulmonary bypass (CPB).

Methods. Fourteen patients with off-pump operations and 18 patients with CPB were compared. Seven patients in the off-pump group underwent a minithoracotomy and received only an arterial graft, whereas 7 patients underwent sternotomy and received both an arterial and one or two vein grafts. S100B was measured in arterial plasma using an immunoassay with enhanced sensitivity.

Results. S100B before the operation was 0.03 μg/L. At wound closure, S100B in patients of the off-pump and CPB groups reached a maximum level of 0.22 ± 0.07 and 2.4 ± 1.5 μg/L, respectively (p < 0.001). No strokes occurred. Patients without CPB receiving arterial and vein grafts released slightly more S100B (p < 0.05) than patients with only arterial grafting. In patients undergoing CPB, S100B increased slightly before aortic cannulation (p < 0.001), to the same level as the maximum reached for the non-CPB group.

Conclusions. Coronary artery bypass grafting with CPB caused a 10-fold greater increase in S100B than off-pump grafting. S100B release after off-pump sternotomy with vein grafting was slightly greater than in arterial grafting through a minithoracotomy.     

S100 in mild traumatic brain injury

Primary objectives: To examine the diagnostic value of S100 in mild traumatic brain injury (MTBI).

Research design: Prospective cohort study.

Methods and procedures: S100B, S100A1B and S100BB concentrations were examined in sera from patients with MTBI with an arrival Glasgow Coma Scale score of 15 or 14, patients with orthopaedic injuries and non-injured subjects.

Main outcome and results: Mean values and proportions of subjects above cut-off limits for S100B and S100A1B were significantly higher in each trauma group than in non-injured controls, but only for S100A1B when patients with MTBI were compared with controls with orthopaedic injuries. Using a 97.5 percentile cut-off limit, the sensitivity of S100A1B for MTBI vs orthopaedic injury was 61% (95% confidence interval (CI) 49-73%), specificity 77% (95% CI 62-93%). The area under the ROC curve did not approach 0.9 for any cut off limit.

Conclusions: Diagnostic validity of S100 in acute MTBI was not demonstrated. S100A1B has merits for long-term prognostic studies.     

Das serologische Protein S100B

Objective

Patients presenting in the emergency department with a mild injury to the head pose a particular challenge due to their high prevalence but low rate of traumatic brain injury. However, missed traumatic brain injuries may result in fatal consequences. Therefore we investigated the diagnostic performance of serological protein S100B measurement in adult patients presenting with mild head injury and a GCS 13-15 to identify traumatic brain injury.

Design and methods

We conducted a systematic review of the literature. Two reviewers screened potential studies for inclusion and independently extracted study data. For all included studies, we applied the QUADAS quality assessment tool for systematic reviews of diagnostic accuracy and abstracted the raw data for every included study. Included studies presented results either in 2x2 contingency tables or provided data allowing their construction.

Results

Of 76 studies identified, 8 met the inclusion criteria. Methodology quality was moderate and all studies fulfilled at least 50% of the QUADAS criteria. Overall, the sensitivity to detect intracranial lesions was 94% (95% CI 88–98%) and specificity was 44% (95% CI 30–58%). The subgroup analysis showed significant differences only between studies with different S100B cutoff values (0.10?μg/l versus >0.10?μg/l). The combined odds ratio was 10.3 (95 CI 4.2–24.9).

Conclusions

Serological protein S100B measurement may be helpful as a screening test to identify patients with higher risk of traumatic brain injury for further diagnostic assessment.     

Alterations of the biomarker S-100B and NSE in patients with acute vertebral spine fractures

Background contextAlthough several publications concerning the use of the biomarkers S100B and neuron-specific enolase (NSE) in vertebral spine fractures in animal experimental studies have proven their usefulness as early indicators of injury severity, there are no clinical reports on their effectiveness as indicators in patients with spinal injuries. As these biomarkers have been examined, with promising results, in patients with traumatic brain injury, there is a potential for their implementation in patients with vertebral spine fractures.PurposeTo investigate the early serum measurement of S100B and NSE in patients with vertebral spine fractures compared with those in patients with acute fractures of the proximal femur.Study designProspective longitudinal cohort study.Patient sampleA cohort of 34 patients admitted over an 18-month period to a single medical center for suspected vertebral spine trauma. Twenty-nine patients were included in the control group.Outcome measuresS100B and NSE serum levels were assessed in different types of vertebral spine fractures.MethodsWe included patients older than 16 years with vertebral spine fractures whose injuries were sustained within 24 hours before admission to the emergency room and who had undergone a brief neurologic examination. Spinal cord injuries (SCIs) were classified as being paresthesias, incomplete paraplegias, or complete paraplegias. Blood serum was obtained from all patients within 24 hours after the time of injury. Serum levels of S100B and NSE were statistically analyzed using Wilcoxon signed-rank test.ResultsS100B serum levels were significantly higher in patients with vertebral spine fractures (p=.01). In these patients, the mean S100B serum level was 0.75 μg/L (standard deviation [SD] 1.44, 95% confidence interval [CI] 0.24, 1.25). The mean S100B serum level in control group patients was 0.14 μg/L (SD 0.11, 95% CI 0.10, 0.19). The 10 patients with neurologic deficits had significantly higher S100B serum levels compared with the patients with vertebral fractures but without neurologic deficits (p=.02). The mean S100B serum level in these patients was 1.18 μg/L (SD 1.96). In the 26 patients with vertebral spine fractures but without neurologic injury, the mean S100B serum level was 0.42 μg/L (SD 0.91, 95% CI 0.08, 0.76). The analysis revealed no significant difference in NSE levels.ConclusionsWe observed a significant correlation not only between S100B serum levels and vertebral spine fractures but also between S100B serum levels and SCIs with neurologic deficit. These results may be meaningful in clinical practice and to future studies.     

Effects of head and extracranial injuries on serum protein S100B levels in trauma patients

BACKGROUND: Serum protein S100B determinations have been recently suggested as markers of traumatic brain injury. However, little is known about the effects of extracranial injuries on S100B levels in trauma patients. METHODS: We studied 224 patients with head trauma (54 of whom also had extracranial injuries), 155 patients with various types of extracranial injuries, and 8 healthy pilots exposed to high Gz forces. The head trauma patients had either no brain injury (n = 35), mild brain injury (n = 165), or moderate to severe brain injury (n = 24). The extracranial injuries were divided into small and large injuries. Serum protein S100B levels were determined from samples taken within 6 hours after the trauma event. RESULTS: The head trauma patients had a significantly higher median S100B (0.17 microg/L) than the patients with extracranial injuries (0.07 microg/L) (p < 0.001). Serum S100B levels also correlated with the severity of brain injury (p < 0.001), the highest values occurring in the patients with moderate to severe brain injury (1.27 microg/L). However, large extracranial injuries also elevated S100B levels (0.35 microg/L), whereas small extracranial injuries in the absence of head trauma did not significantly affect S100B levels (0.07 microg/L). Above the cutoff level of 0.13 microg/L, there were 61% of the head trauma patients and 26% of those with extracranial injuries (Pearson chi test, p < 0.001). However, only 4% of the patients with purely extracranial injuries had a concentration of S100B above the cutoff level of 0.50 microg/L, whereas the head trauma patients with moderate to severe brain injury exceeded this cutoff in 67% of the cases. Exposure to high Gz forces did not influence serum S100B levels in healthy individuals. CONCLUSION: We conclude that serum S100B is a sensitive marker of brain injury, which correlates with the severity of the injury. Large extracranial injuries also elevate S100B levels. However, S100B has a high negative predictive power, and the finding of a normal S100B value shortly after trauma should thus exclude significant brain injury with a high accuracy.     

Brain tissue oxygen response in severe traumatic brain injury

Summary ?Objective. To investigate clinical relevance and prognostic value of brain tissue oxygen response (TOR: response of brain tissue pO₂ to changes in arterial pO₂) in traumatic brain injury (TBI). Patients and methods. In a prospective cohort study TOR was investigated in 41 patients with severe TBI (Glasgow Coma Score ≤8) in whom continuous monitoring of brain tissue oxygen pressure (PbrO₂) was performed. TOR was investigated each day over a five day period for 15 minutes by increasing FiO₂ on the ventilator setting. FiO₂ was increased directly from baseline to 1.0 for a period of 15 minutes under stable conditions (145 tests). In 34 patients the effect of decreasing PaCO₂ was evaluated on TOR by performing the same test after increasing inspiratory minute volume on the ventilator setting to 20% above baseline. Arterial blood gas analysis was performed before and after changing ventilator settings. Multimodality monitoring, including PbrO₂ was performed in all patients. Outcome at six months was evaluated according to the Glasgow Outcome Scale. For statistical analysis the Mann-whitney U-test was used for ordinally distributed variables, and the Chi-square test for categorical variables. Predictive value of TOR was analyzed in a multivariable model. Results. 145 tests were available for analysis. Baseline PbrO₂ varied from 4.0 to 50 mmHg at PaO₂ values of 73–237 mmHg. At FiO₂ settings of 1.0, PbrO₂ varied from 9.1–200 mmHg and PaO₂ from 196–499 mmHg. Three distinct patterns of response were noted: response type A is characterized by a sharp increase in PbrO₂, reaching a plateau within several minutes; type B by the absence of a plateau, and type C by a short plateau phase followed by a subsequent further increase in PbrO₂. Patterns characterized by a stable plateau (type A), considered indicative of intact regulatory mechanisms, were seen more frequently from 48 hours after injury on. If present within the first 24 hours after injury such a response was related to more favorable outcome (p = 0.06). Mean TOR of all tests was 0.73 ± 0.59 with an median TOR of 0.58. Patients with an unfavourable outcome had a higher TOR (1.03 ± 0.60) during the first 24 hours, compared to patients with a favorable outcome (0.61 ± 0.51; p = 0.02). Multiple logistic regression analysis supported the independent predictive value of tissue oxygen response for unfavorable outcome (odds ratio 4.8). During increased hyperventilation, mean TOR decreased substantially from 0.75 ± 0.54 to 0.65 ± 0.45 (p = 0.06; Wilcoxon test). Within the first 24 hours after injury a decrease in TOR following hyperventilation was significantly related to poorer outcome (p = 0.01). Conclusions. Evaluation of TOR affords insight in (disturbances in) oxygen regulation after traumatic brain injury, is of prognostic value and may aid in identifying patients at (increased) risk for ischemia. Published online June 11, 2003     

Intraventricular infusion of the neurotrophic protein S100B improves cognitive recovery after fluid percussion injury in the rat

Elevated serum S100B levels have been shown to be a predictor of poor outcome after traumatic brain injury (TBI). Experimental data, on the other hand, demonstrate a neuroprotective and neurotrophic effect of this calcium-binding protein. The purpose of this study was to examine the role of increased S100B levels on functional outcome after TBI. Following lateral fluid percussion or sham injury in male Sprague Dawley rats (n = 56), we infused S100B (50 ng/h) or vehicle into the cerebrospinal fluid of the ipsilateral ventricle for 7 days using an osmotic mini-pump. Assessment of cognitive performance by the Morris water maze on days 30-34 after injury revealed an improved performance of injured animals after S100B infusion (p < 0.05), when compared to vehicle infusion. Blood samples for analysis of clinical markers of brain damage, S100B and neuron specific enolase, taken at 30 min, 3 h, 4 h, 2 days, or 5 days showed a typical peak 3 h after injury (p < 0.01), and higher serum levels correlated significantly with an impaired cognitive recovery (p < 0.01). The correlation of higher serum S100B levels with poor water maze performance may result from injury induced opening of the blood-brain barrier, allowing the passage of S100B into serum. Thus while higher serum levels of S100B seem to reflect the degree of blood-brain barrier opening and severity of injury, a beneficial effect of intraventricular S100B administration on long-term functional recovery after TBI has been demonstrated for the first time. The exact mechanism by which S100B exerts its neuroprotective or neurotrophic influence remains unknown and needs to be elucidated by further investigation.     

A critical analysis of the role of the neurotrophic protein S100B in acute brain injury

We provide a critical analysis of the relevance of S100B in acute brain injury emphazising the beneficial effect of its biological properties. S100B is a calcium-binding protein, primarily produced by glial cells, and exerts auto- and paracrine functions. Numerous reports indicate, that S100B is released after brain insults and serum levels are positively correlated with the degree of injury and negatively correlated with outcome. However, new data suggest that the currently held view, that serum measurement of S100B is a valid "biomarker" of brain damage in traumatic brain injury (TBI), does not acknowlege the multifaceted release pattern and effect of the blood-brain barrier disruption upon S100B levels in serum. In fact, serum and brain S100B levels are poorly correlated, with serum levels dependent primarily on the integrity of the blood-brain barrier, and not the level of S100B in the brain. The time profile of S100B release following experimental TBI, both in vitro and in vivo, suggests a role of S100B in delayed reparative processes. Further, recent findings provide evidence, that S100B may decrease neuronal injury and/or contribute to repair following TBI. Hence, S100B, far from being a negative determinant of outcome, as suggested previously in the human TBI and ischemia literature, is of potential therapeutic value that could improve outcome in patients who sustain various forms of acute brain damage.     

High serum S100B levels for trauma patients without head injuries

OBJECTIVE: Studies of patients with head trauma have demonstrated a correlation between a serum marker of brain tissue damage, namely S100B, and neuroradiological findings. It was recently demonstrated that the increases in serum S100B levels after heart surgery have extracerebral origins, probably surgically traumatized fat, muscle, and bone marrow. The current study examined multitrauma patients without head trauma, to determine whether soft-tissue and bone damage might confound the interpretation of elevated serum S100B concentrations for patients after head trauma. METHODS: A commercial assay was used to determine serum S100B concentrations for a normal population (n = 459) and multitrauma patients without head injury (n = 17). Concentrations of the two subtypes of S100B (S100A1B and S100BB) were determined using separate noncommercial assays. RESULTS: The mean serum S100B concentration for a normal healthy population was 0.032 microg/L (median, 0.010 microg/L; standard deviation, 0.040 microg/L). The upper 97.5% and 95% reference limits were 0.13 and 0.10 microg/L, respectively. No major age or sex differences were observed. Among trauma patients, serum S100B levels were highest after bone fractures (range, 2-10 microg/L) and thoracic contusions without fractures (range, 0.5-4 microg/L). Burns (range, 0.8-5 microg/L) and minor bruises also produced increased S100B levels. S100A1B and S100BB were detected in all samples. CONCLUSION: Trauma, even in the absence of head trauma, results in high serum concentrations of S100B. Interpretation of elevated S100B concentrations immediately after multitrauma may be difficult because of extracerebral contributions. S100B may have a negative predictive value to exclude brain tissue damage after trauma. Similarly, nonacute S100B measurements may be of greater prognostic value than acute measurements.