[A case of meningeal melanomatosis diagnosed by immunostaining of cerebrospinal fluid].

A 49-year-old woman was admitted to our hospital with suspected hypertensive encephalopathy. On the basis of MRI showing leptomeningeal enhancement and Class V cytology of the CSF, she was diagnosed as having leptomeningeal carcinomatosis. Although no primary site was detected, a few melanin granules were observed at the third CSF examination. The atypical cells in the CSF demonstrated immunoreactivity for HMB-45 and S-100, which are specific markers of malignant melanoma. There have been few reports of meningeal melanomatosis in Japan. This case illustrates that immunostaining is diagnostically useful in patients with leptomeningeal carcinomatosis from neoplasms with unknown primary sites.

Could Cerebrospinal Fluid Biomarkers Offer Better Predictive Value for Spinal Cord Ischaemia Than Current Neuromonitoring Techniques During Thoracoabdominal Aortic Aneurysm Repair - A Systematic Review.

OBJECTIVE: Cerebrospinal fluid (CSF) drainage is a technique that has significantly reduced the incidence of spinal cord ischaemia (SCI). We present results of a systematic review to assess the literature on this topic in relation to thoracoabdominal aortic aneurysm repair (TAAR). METHODS: Major medical databases were searched to identify papers related to CSF biomarkers measured during TAAAR. RESULTS: Fifteen papers reported measurements of CSF biomarkers with 265 patients in total. CSF biomarkers measured included S-100ß, neuron-specific endolase (NSE), lactate, glial fibrillary acidic protein A (GFPa), Tau, heat shock protein 70 and 27 (HSP70, HSP27), and proinflammatory cytokines. Lactate and S-100ß were reported the most, but did not correlate with SCI, which was also the case with NSE and TAU. GFPa showed significant CSF level rises, both intra and postoperative in patients who suffered SCI and warrants further investigation, similar results were seen with HSP70, HSP27 and IL-8. CONCLUSIONS: Although there is significant interest in this topic, there still remains a significant lack of high-quality studies investigating CSF biomarkers during TAAR to detect SCI. A large and multicentre study is required to identify the significant role of each biomarker.

Could cerebrospinal fluid biomarkers offer better predictive value for spinal cord ischaemia than current neuromonitoring techniques during thoracoabdominal aortic aneurysm repair - a systematic review

Abstract Objective: Cerebrospinal fluid (CSF) drainage is a technique that has significantly reduced the incidence of spinal cord ischaemia (SCI). We present results of a systematic review to assess the literature on this topic in relation to thoracoabdominal aortic aneurysm repair (TAAR). Methods: Major medical databases were searched to identify papers related to CSF biomarkers measured during TAAAR. Results: Fifteen papers reported measurements of CSF biomarkers with 265 patients in total. CSF biomarkers measured included S-100ß, neuron-specific endolase (NSE), lactate, glial fibrillary acidic protein A (GFPa), Tau, heat shock protein 70 and 27 (HSP70, HSP27), and proinflammatory cytokines. Lactate and S-100ß were reported the most, but did not correlate with SCI, which was also the case with NSE and TAU. GFPa showed significant CSF level rises, both intra and postoperative in patients who suffered SCI and warrants further investigation, similar results were seen with HSP70, HSP27 and IL-8. Conclusions: Although there is significant interest in this topic, there still remains a significant lack of high-quality studies investigating CSF biomarkers during TAAR to detect SCI. A large and multicentre study is required to identify the significant role of each biomarker.

Axonal damage is remarkable in patients with acutely worsening symptoms of compression myelopathy: biomarkers in cerebrospinal fluid samples.

PURPOSE: To determine levels of biomarkers reflecting damage to axon, myelin, astrocytes, and neuron in cerebrospinal fluid (CSF) of patients with cervical compression myelopathy. METHODS: We collected 69 CSF samples from patients before spinal surgery for acutely worsening compression myelopathy (AM, 20), chronic compression myelopathy (CM, 20), and lumbar canal stenosis (LCS 29; control). We measured levels of phosphorylated neurofilament subunit H (pNF-H), tau (reflecting axonal damage), myelin basic protein (MBP) (reflecting demyelination), S100b (reflecting astrocyte damage), and neuron-specific enolase (NSE) (reflecting neuronal damage). Change of neurological function by surgery was determined using a Japanese Orthopaedic Association (JOA) score for cervical myelopathy. RESULTS: Significantly higher levels of pNF-H were detected in AM compared with those in either CM or LCS (P < 0.01). Significantly higher levels of tau were detected in AM compared with those in CM (P < 0.05). Levels of MBP were undetectable in almost all the patients. Levels of S100b were equivalent in the three groups. Levels of NSE in AM and CM were significantly lower than those in LCS (P < 0.01). The recovery rate of JOA score was significantly greater for patients with AM than CM. We found a positive correlation between pNF-H and recovery of JOA score (r = 0.381, P = 0.018). CONCLUSION: The present results suggest that axonal damage is remarkable compared with demyelination, astrocytic, and neuronal damage in AM. Better clinical outcome in AM with high CSF levels of pNF-H indicates that axonal compensatory plasticity in spinal cord is preserved, and pNF-H can be predictive of good surgical outcome for AM. These slides can be retrieved under Electronic Supplementary Material.

LEVELS OF NEUROSPECIFIC MARKERS IN CEREBROSPINAL FLUID OF ADULT PATIENTS WITH BACTERIAL MENINGITIS.

At present, the great attention is given to the neurospecific markers as their elevated level in the cerebrospinal fluid corresponds to the degree of destruction of relevant CNS cells. Therefore, actual direction of the studies of the pathogenesis and diagnosis of CNS diseases is to determine levels of neurospecific markers in the cerebrospinal fluid (CSF). The purpose of the study was to evaluate the diagnostic and prognostic role of NSE, S-100 protein, GFAP and MBP levels in CSF of patients with acute bacterial meningitis. S-100 protein, NSE, GFAP and MBP levels in CSF of patients with acute pneumococcal and meningococcal meningitis were determined during admission and after 10-12 days of treatment. Patients were divided into groups depending on the etiology and severity of the disease. 60 cases of acute bacterial meningitis, as a study group, and 12 cases with acute respiratory infection and meningism, as a control group, were analyzed. It is shown that CSF levels of NSE, S-100 protein, GFAP and MBP on the first day of admission were significantly increased (P<0,05), depending on the severity of the disease. The highest levels of neurospecific markers have been identified in non-survivors (P<0,001). The concentration changes of CSF neurospecific markers are found to be helpful as a diagnostic and prognostic marker in acute bacterial meningitis.

Decreased level of sRAGE in the cerebrospinal fluid of multiple sclerosis patients at clinical onset.

OBJECTIVES: Receptor for advanced glycation end products (RAGE) ligands/RAGE interactions have been proposed to have a pathogenic role in neuroinflammatory disorders. Our study aimed to assess changes in high-mobility group box (HMGB)1 and its receptor RAGE in peripheral blood (PBL) and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) at the disease onset compared with control subjects. METHODS: PBL and CSF were collected from control subjects (n = 30) and MS patients (n = 27) at clinical onset. Soluble RAGE (sRAGE), HMGB1, S100 calcium-binding protein A12 (S100A12), interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were measured in the CSF and plasma by enzyme-linked immunosorbent assay. Gene expression in PBL mononuclear cells (PBMCs) was detected by quantitative PCR for RAGE, HMGB1, S100A12 and several proinflammatory/immunoregulatory cytokines. RESULTS: We found a significantly lower expression of IL-10 (p = 0.031) in the PBMCs of MS patients. The level of sRAGE in the CSF of MS patients was lower (p = 0.021), with the ability to discriminate between MS patients and control subjects. Moreover, PBMC gene expression for HMGB1 and S100A12 positively correlated with IL-6. CONCLUSIONS: Our study confirmed that the cytokine network is disturbed in PBL and CSF at MS clinical onset. The deregulated HMGB1/RAGE axis found in our study may present an early pathogenic event in MS, proposing sRAGE as a possible novel therapeutic strategy for MS treatment.

S100 and S100ß: biomarkers of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass.

OBJECTIVE: The present study is to describe the clinical impact of S100 and S100ß for the evaluation of cerebral damage in cardiac surgery with or without the use of cardiopulmonary bypass (CPB). METHODS: Quantitative results of S100 and S100ß reported in the literature of the year range 1990-2014 were collected, screened and analyzed. RESULTS: Cerebrospinal fluid and serum S100 levels showed a same trend reaching a peak at the end of CPB. The cerebrospinal fluid/serum S100 ratio decreased during CPB, reached a nadir at 6 h after CPB and then increased and kept high untill 24 h after CPB. Serum S100 at the end of CPB was much higher in infant than in adults, and in on-pump than in off-pump coronary artery bypass patients. ∆S100 increased with age and CPB time but lack of statistical significances. Patients receiving an aorta replacement had a much higher ∆S100 than those receiving a congenital heart defect repair. Serum S100ß reached a peak at the end of CPB, whereas cerebrospinal fluid S100 continued to increase and reached a peak at 6 h after CPB. The cerebrospinal fluid/serum S100ß ratio decreased during CPB, increased at the end of CPB, peaked 1 h after CPB, and then decreased abruptly. The increase of serum S100ß at the end of CPB was associated with type of operation, younger age, lower core temperature and cerebral damages. ∆S100ß displayed a decreasing trend with age, type of operation, shortening of CPB duration, increasing core temperature, lessening severity of cerebral damage and the application of intervenes. Linear correlation analysis revealed that serum S100ß concentration at the end of CPB correlated closely with CPB duration. CONCLUSION: S100 and S100ß in cerebrospinal fluid can be more accurate than in the serum for the evaluations of cerebral damage in cardiac surgery. However, cerebrospinal fluid biopsies are limited. But serum S100ß and ∆S100ß seem to be more sensitive than serum S100 and ∆S100. The cerebral damage in cardiac surgery might be associated with younger age, lower core temperature and longer CPB duration during the operation. Effective intervenes with modified CPB circuit filters or oxygenators and supplemented anesthetic agents or priming components may alleviate the cerebral damage.

Expression and function of psoriasin (S100A7) and koebnerisin (S100A15) in the brain.

The expression and function of psoriasin in the brain have been insufficiently characterized. Here, we show the induction of psoriasin expression in the central nervous system (CNS) after bacterial and viral stimulation. We used a pneumococcal meningitis in vivo model that revealed S100A15 expression in astrocytes and meningeal cells. These results were confirmed by a cell-based in vivo assay using primary rat glial and meningeal cell cultures. We investigated psoriasin expression in glial and meningeal cells using polyinosinic-polycytidylic acid, a synthetic analog of double-stranded RNA that mimics viral infection. Furthermore, previous results showed that antimicrobial peptides have not only bactericidal but also immunomodulatory functions. To test this statement, we used recombinant psoriasin as a stimulus. Glial and meningeal cells were treated with recombinant psoriasin at concentrations from 25 to 500 ng/ml. Treated microglia and meningeal cells showed phosphorylation of the extracellular signal-regulated kinase 1 (ERK1)/ERK2 (ERK1/2) signal transduction pathway. We demonstrated that this activation of ERK depends on RAGE, the receptor for advanced glycation end products. Furthermore, microglia cells treated with recombinant psoriasin change their phenotype to an enlarged shape. In conclusion, our results indicate an occurrence of psoriasin in the brain. An involvement of psoriasin as an antimicrobial protein that modulates the innate immune system after bacterial or viral stimulation is possible.

Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy.

BACKGROUND: Acute encephalitis/encephalopathy (AEE) is a devastating cause of severe neurodevelopmental sequelae or death in children. Assessing ongoing brain injury and predicting outcomes using bedside point-of-care testing is expected to be extremely valuable. METHODS: For this study, three brain injury markers, S-100B, glial fibrillary acidic protein (GFAP), and tau protein, were measured in early cerebrospinal fluid samples of children with AEE. Subjects comprised three groups: Group 1 (non-AEE control, n = 27); Group 2 (AEE with normal resolution or mild sequelae, n = 13); and Group 3 (AEE with severe sequelae or death, i.e. "poor outcome," n = 10). RESULTS: All marker levels were significantly higher in Group 3 than in Group 1 or 2. In Group 3, only S-100B was significantly higher in non-survivors than in survivors. For scoring assessment (range: 0-3 points), the predictive accuracies of 3 points for poor outcomes in children with AEE (i.e. Group 2 and 3, n = 23) were 91% (21/23) for S-100B, 74% (17/23) for GFAP, and 78% (18/23) for tau. When the scores were summed up for S-100B, GFAP, and tau (range: 0-9 points), and for S-100B and tau (range: 0-6 points), the patients with poor outcomes were identified more accurately using the respective thresholds of 6 points and 4 points (96% [22/23] and 100% [23/23], respectively). CONCLUSION: Our findings suggest that combined measurement and scoring assessment of the markers, especially S-100B and tau, show promise as predictors of clinical outcomes in children with AEE.

Marked increase of the astrocytic marker S100B in the cerebrospinal fluid of HIV-infected patients on LPV/r-monotherapy.

OBJECTIVE: To determine changes of cerebrospinal fluid (CSF) biomarkers of patients on monotherapy with lopinavir/ritonavir. DESIGN: The Monotherapy Switzerland/Thailand study (MOST) trial compared monotherapy with ritonavir-boosted lopinavir with continued therapy. The trial was prematurely stopped due to virological failure in six patients on monotherapy. It, thus, offers a unique opportunity to assess brain markers in the early stage of HIV virological escape. METHODS: : Sixty-five CSF samples (34 on continued therapy and 31 on monotherapy) from 49 HIV-positive patients enrolled in MOST. Using enzyme-linked immunosorbent assay, we determined the CSF concentration of S100B (astrocytosis), neopterin (inflammation), total Tau (tTau), phosphorylated Tau (pTau), and amyloid-ß 1-42 (Aß), the latter three indicating neuronal damage. Controls were CSF samples of 29 HIV-negative patients with Alzheimer dementia. RESULTS: In the CSF of monotherapy, concentrations of S100B and neopterin were significantly higher than in continued therapy (P = 0.006 and P = 0.013, respectively) and Alzheimer dementia patients (P < 0.0001 and P = 0.0005, respectively). In Alzheimer dementia, concentration of Aß was lower than in monotherapy (P = 0.005) and continued therapy (P = 0.016) and concentrations of tTau were higher than in monotherapy (P = 0.019) and continued therapy (P = 0.001). There was no difference in pTau among the three groups. After removal of the 16 CSF with detectable viral load in the blood and/or CSF, only S100B remained significantly higher in monotherapy than in the two other groups. CONCLUSION: Despite full viral load-suppression in blood and CSF, antiretroviral monotherapy with lopinavir/ritonavir can raise CSF levels of S100B, suggesting astrocytic damage.

The value of the calcium binding protein S100 in the management of patients with traumatic brain injury.

BACKGROUND: From the first study in 1995 the role of calcium-binding protein S100B in Traumatic Brain Injury (TBI) has been variously investigated in many clinical works. The aim of this work is to analyze the recent published reports with a reference to serum and CSF levels and to identify a possible role of S100 in the management ofTBI. METHODS: A MEDLINE search with a various number of query related to "S100" and "TBI" was performed from 2000 to 2011. All identified articles and abstracts have been reviewed. RESULTS: Serum and CSF samples of the marker well correlate in most of the papers to the degree of intracranial injury as determined by CT scans. Furthermore patients with the higher levels of S100B show a worse prognosis. In the paediatric age a relationship with the outcomes in spite of difficulties to determine normal values is also observed. Some proposal about a clinical use of S100B to decrease the number of neuroradiological examinations are present. CONCLUSIONS: S100B shows some interesting potentialities, but we have not enough evidence to insert this marker of brain damage in the protocols for management of TBI. However its use in experts' hands in association with others clinical and radiological features may help to improve medical practice in the treatment of TBI.

Cerebrospinal fluid S100B levels reflect symptoms of depression in patients with non-inflammatory neurological disorders.

Recent findings document numerous interactions between neuronal and glial systems that likely play a role in the pathophysiology of depression. These findings suggest that glia-derived neurotrophic protein S100B may play a significant role in developing depression. To test the relationship between S100B and depressive symptoms we designed cross-sectional clinical study including S100B serum and CSF levels in neurological patients with non-inflammatory disorders (NIND), who undergone cerebrospinal fluid assessment for diagnostic purposes. The present study was focused on psychometric testing of depression (BDI-II), anxiety (SAS) and alexithymia (TAS-20), and neurochemical measure of cerebrospinal fluid (CSF) and serum levels of S100B in 40 NIND inpatients [mean age 41.67]. The main result shows that S100B in CSF is significantly negatively correlated with BDI-II (Spearman R=-0.51, p<0.0009) but not with SAS and TAS-20. The finding indicates that decreased level of S100B in CSF is related to increased symptoms of depression in the NIND patients.

[The biochemical markers of hypoxic perinatal affections of central nervous system in newborns].

The review analyses the clinical informativity of new biochemical markers of perinatal hypoxic affection of central nervous system in newborns--xanthine, hypoxanthine, adrenomedillin, protein S100B, activin A and neuron specific enolase.

CSF-biomarkers in Olympic boxing: diagnosis and effects of repetitive head trauma.

BACKGROUND: Sports-related head trauma is common but still there is no established laboratory test used in the diagnostics of minimal or mild traumatic brain injuries. Further the effects of recurrent head trauma on brain injury markers are unknown. The purpose of this study was to investigate the relationship between Olympic (amateur) boxing and cerebrospinal fluid (CSF) brain injury biomarkers. METHODS: The study was designed as a prospective cohort study. Thirty Olympic boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in the study. CSF samples were collected by lumbar puncture 1-6 days after a bout and after a rest period for at least 14 days. The controls were tested once. Biomarkers for acute and chronic brain injury were analysed. RESULTS: NFL (mean ± SD, 532±553 vs 135±51 ng/L p = 0.001), GFAP (496±238 vs 247±147 ng/L p<0.001), T-tau (58±26 vs 49±21 ng/L p<0.025) and S-100B (0.76±0.29 vs 0.60±0.23 ng/L p = 0.03) concentrations were significantly increased after boxing compared to controls. NFL (402±434 ng/L p = 0.004) and GFAP (369±113 ng/L p = 0.001) concentrations remained elevated after the rest period. CONCLUSION: Increased CSF levels of T-tau, NFL, GFAP, and S-100B in >80% of the boxers demonstrate that both the acute and the cumulative effect of head trauma in Olympic boxing may induce CSF biomarker changes that suggest minor central nervous injuries. The lack of normalization of NFL and GFAP after the rest period in a subgroup of boxers may indicate ongoing degeneration. The recurrent head trauma in boxing may be associated with increased risk of chronic traumatic brain injury.

Effects of hypothermia on NSE and S-100 protein levels in CSF in neonates following hypoxic/ischaemic brain damage.

AIM: The aim of the study was to evaluate the effects of hypothermia on neuron-specific enolase (NSE) and S-100 protein levels in cerebrospinal fluid (CSF) in neonates with hypoxic/ischaemic encephalopathy (HIE). METHODS: Fifty-one enrolled neonates with HIE were divided into two groups: hypothermia (n = 23) and control (n = 28). NSE and S-100 protein were measured with immunoradiometric assays. Amino acid neurotransmitters were also measured by reversed-phase high-performance liquid chromatography. Neurodevelopmental assessments were performed at 3 and 12 months of age. RESULTS: Neuron-specific enolase and S-100 levels were lower, and neurodevelopment outcome was better in the hypothermia group compared with the control group. Among the infants who received hypothermia, CSF NSE and S-100 were significantly higher in those who developed severe neurological impairment (mental development index or physical development index <70). There were no significant differences between the two groups in amino acid neurotransmitters. CONCLUSION: These results indicated that hypothermia was associated with decreased CSF NSE and S-100 level and correlated with neurodevelopmental outcome in infants with HIE.

Shunt-dependent hydrocephalus following subarachnoid hemorrhage correlates with increased S100B levels in cerebrospinal fluid and serum.

Posthemorrhagic hydrocephalus requiring permanent ventriculoperitoneal shunt placement is a major complication of aneurysmal subarachnoid hemorrhage (SAH). High S100B serum and cerebrospinal fluid (CSF) levels are considered to reflect the severity of brain injury. We prospectively assessed whether S100B levels in serum and CSF were predictive parameters for permanent shunt requirement following aneurysmal SAH. In patients suffering from aneurysmal SAH and treated with an external ventricular drain (EVD), S100B levels in serum and CSF were measured daily as long as the EVD was in place. S100B levels of patients who passed their EVD challenge were compared with those patients who required a permanent ventriculoperitoneal shunt placement. Out of 68 patients included in the study, 43 patients (63.2%) passed the EVD challenge and in 25 patients (36.8%) permanent ventriculoperitoneal shunting was performed. Group comparison revealed that in patients who required shunt placement, S100B was significantly higher in CSF (p < 0.05 at days 2, 4, 6, 10; p < 0.005 at days 1, 3, 5, 7, 8, 9) and serum (p < 0.05 at days 4-7) compared with patients who could be weaned from the EVD. Assessment of S100B levels in CSF and serum may be useful as a predictive parameter for shunt dependency in patients with posthemorrhagic hydrocephalus following aneurysmal SAH.

Prediction of the neurological outcome with intrathecal high mobility group box 1 and S100B in cardiac arrest victims: a pilot study.

OBJECTIVES: To investigate whether high mobility group box 1 (HMGB1) and S100B in cerebrospinal fluid (CSF) and the serum predict the neurological outcome in patients resuscitated from out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: This study was designed as a prospective observational study. Twenty-five patients, who received standard cardiopulmonary resuscitation and post-resuscitation intensive care, were enrolled in this study. The patients were divided into two groups according to Glasgow-Pittsburgh Cerebral Performance categories (CPCs) at 6 months after return of spontaneous circulation (ROSC), Group G (n = 7, CPC 1 or 2) and Group P (n = 18, CPC ≥ 3). Their blood samples were taken at 6, 24, and 48h after ROSC. The patients, whose CSF was sampled at 48h, were also divided into either sub-Group G (n = 6) or sub-Group P (n = 8) at 6 months after ROSC. RESULTS: HMGB1 and S100B in CSF in sub-Group P were significantly higher than those in sub-Group G (HMGB1, <1.0 vs. 12.4 ng/ml, P = 0.009; S100B, 2.68 vs. 84.2 ng/ml, P = 0.007, respectively). HMGB1 in CSF was strongly correlated with S100B (σ = 0.81, P = 0.001). HMGB1 was elevated in serum at 6h and normalized within 48 h after ROSC without any significant differences between the two groups. Serum S100B in Group P was significantly higher than that in Group G at each time point. CONCLUSIONS: The significant elevations of HMGB1 and S100B in CSF, and S100B in serum are associated with the neurologically poor outcome in OHCA patients.

S100B proteins in febrile seizures.

S100B protein concentrations correlate with the severity and outcome of brain damage after brain injuries, and have been shown to be markers of blood-brain barrier damage. In children elevated S100B values are seen as a marker of damage to astrocytes even after mild head injuries. S100B proteins may also give an indication of an ongoing pathological process in the brain with respect to febrile seizures (FS) and the likelihood of their recurrence. To evaluate this, we measured S100B protein concentrations in serum and cerebrospinal fluid from 103 children after their first FS. 33 children with acute infection without FS served as controls for the serum concentrations. In the FS patients the mean S100B concentration in the cerebrospinal fluid samples was 0.21 µg/L and that in the serum samples 0.12 µg/L. The mean serum concentration in the controls was 0.11 µg/L (difference 0.01 µg/L, 95% confidence interval -0.02 to 0.04 µg/L, P = 0.46). There was a correlation between age and serum S100B concentration (r = -0.28, P = 0.008) in children under four years, but S100B concentrations did not predict the clinical severity of the FS nor their recurrence. There was no correlation between time of arrival at the hospital after FS and S100B concentration in serum (r = -0.130, P = 0.28) or in cerebrospinal fluid samples (r=-0.091, P = 0.52). Our findings indicate that FS does not cause significant blood-brain barrier openings, and increase the evidence that these seizures are relatively harmless for the developing brain.

Elevated S100B level in cerebrospinal fluid could predict poor outcome of carbon monoxide poisoning.

OBJECTIVE: S100B is a calcium-binding protein produced by astroglia in the brain and has been used as a marker of neuronal damage after brain trauma. We investigated the utility of S100B in cerebrospinal fluid (CSF) measured during the early phase of carbon monoxide (CO) poisoning in predicting the subsequent clinical course. METHODS: The study included 31 patients who were admitted to the hospital with loss of consciousness following CO poisoning. S100B levels were measured by enzyme-linked immunosorbent assay in CSF, and serum samples collected simultaneously within 24 hours and on the fourth day after CO exposure. All patients were followed for at least 3 months and divided into 3 groups based on the clinical course: persistent vegetative state (PVS), delayed encephalopathy (DE), and complete recovery with no complications (NC). RESULTS: During the 3-month period, 3 patients developed PVS, 5 developed DE, and 23 were classified as NC. The mean S100B levels in the CSF within 24 hours after CO exposure were higher in the PVS group (9.25 ng/mL) than in the DE (2.03 ng/mL) and NC groups (1.86 ng/mL). However, the mean serum S100B levels were not elevated in the 3 groups (0.21, 0.59, and 0.16 ng/mL, respectively). CONCLUSION: Early elevation of S100B in CSF after CO poisoning could be a suitable predictor of subsequent development of PVS.

Neuroglial alterations in rats submitted to the okadaic acid-induced model of dementia.

Several types of animal models have been developed to investigate Alzheimer's disease (AD). Okadaic acid (OA), a potent inhibitor of phosphatases 1 and 2A, induces characteristics that resemble AD-like pathology. Memory impairment induced by intra-hippocampal injection of OA has been reported, accompanied by remarkable neuropathological changes including hippocampal neurodegeneration, a paired helical filament-like phosphorylation of tau protein, and formation of ß-amyloid containing plaque-like structures. Rats were submitted to bilateral intrahippocampal okadaic acid-injection (100 ng) and, 12 days after the surgery, behavioral and biochemical tests were performed. Using this model, we evaluated spatial cognitive deficit and neuroglial alterations, particularly astroglial protein markers such as glial fibrillary acidic protein (GFAP) and S100B, metabolism of glutamate, oxidative parameters and alterations in MAPKs. Our results indicate significant hippocampal changes, including increased GFAP, protein oxidation, and phosphorylation of p38(MAPK); and decreases in glutathione content, transporter EAAT2/GLT-1, and glutamine synthetase activity as well as a decrease in cerebrospinal fluid S100B. No alterations were observed in glutamate uptake activity and S100B content. In conclusion, the OA-induced model of dementia caused spatial cognitive deficit and oxidative stress in this model and, for the first time to our knowledge, specific astroglial alterations. Findings contribute to understanding diseases accompanied by cognitive deficits and the neural damage induced by AO administration.