S100beta Protein Research Articles

Clinical significance of serum S-100 beta protein level after pediatric cardiac surgery.

The serum S-100 beta protein level is a specific marker of damage to the central nerve system (CNS). We studied its significance in pediatric cardiac surgery as a possible marker of CNS damage. Subjects were 18 consecutive pediatric patients aged 12 days to 13 years (mean: 2.8 years) undergoing open-heart surgery. We measured the serum S-100 beta protein level using ELISA (SRL Co. Ltd., Tokyo) immediately after inducing anesthesia and immediately, 12 hours, and 24 hours after weaning from cardiopulmonary bypass (CPB). None had postoperative neurological symptoms. The prebypass serum S-100 beta protein level showed a significant logarithmic correlation with patient age. All patients showed increased S-100 beta protein immediately after weaning from CPB, and multiple regression analysis showed that bypass time and cyanosis were significant factors in such as increase. Cyanosis was the only factor in increased S-100 beta protein levels 12 and 24 hours after weaning from CPB. The peak S-100 beta protein level showed a significant exponential correlation with bypass time. Serum S-100 beta protein elevated immediately after weaning from CPB correlated with bypass time but not with neurological symptoms. Physiological changes other than substantial brain damage caused by CPB may increase the serum S-100 beta protein level. Prebypass data on neonates and infants showed serum S-100 beta protein increased without brain damage supporting this hypothesis.

Biochemical markers of cerebrovascular injury in sleep apnoea syndrome.

Sleep apnoea syndrome (SAS) is a known risk factor for vascular diseases and stroke. Structural brain damage, manifesting as an overt neurological deficit or more subtly as cognitive dysfunction, is a frequent symptom in SAS. The presence of a biochemical marker of cerebral injury would be of great benefit in SAS to screen for even small brain damage and to monitor efficiacy of therapy. Therefore, in 10 patients with mild SAS (age 50.8+/-9.9 yrs, respiratory disturbance index (RDI) 18+/-3.6, lowest arterial oxygen saturation (min Sa,O2) 80.5+/-4.06%) and nine patients with severe SAS (age 50.3+/-11.5 yrs, RDI 75.4+/-21.7, min Sa,O2 56.56+/-14.58%), serum concentrations of neuron-specific enolase (NSE), S-100beta protein, and beta-trace were measured just before and after sleep using commercially available assays. Only serum levels in the normal range could be found, independent of when the blood was taken or the degree of SAS. Structural cerebral injury caused by sleep apnoea syndrome in patients without neurological symptoms or previous cerebrovascular events may be too small to produce a measurable increase in S-100beta, neuron-specific enolase and beta-trace serum concentrations or subclinical cerebral damage may be outside the lower detection limits of the analytical methods which were used. There is a need for biochemical markers and more sensitive methods for detecting small cerebral injury in sleep apnoea syndrome.

Alcohol exposure during adulthood induces neuronal and astroglial alterations in the hippocampal CA-1 area.

Ethanol (ETOH) exposure can result in neuronal damage. Astrocytes are morphologic and functionally related to neurons, and astrocyte-neuron interactions provide strategic sites for the actions of many chemical compounds. The aim of the present work was to study the morphologic alterations of glial cells and neurons on the hippocampus after long-term ETOH exposure using GFAP and S-100 beta protein, neurofilaments of 200 kDa (Nf200), MAP2, and serotonin transporter (5HT-T) immunocytochemical staining. Adult Wistar male rats (200-250 g) were orally exposed to ETOH (6.6% v/v ad libitum) for 6 weeks. Control rats received water ad libitum. Brain sections from control and exposed rats were processed by immunocytochemistry. After ETOH exposure we observed in the CA1 area of the hippocampus: (1) an important astroglial reaction evidenced by the presence of GFAP(+) reactive astrocytes; (2) an increase in S-100 beta immunostaining in astroglial cells; and (3) a decrease in Nf200, 5HT-T, and MAP2 immunoreactivity. The current study provides evidence that long-term ETOH exposure induces alterations in the neuronal cytoskeleton and an astroglial reaction, which is a common response to brain injury and may promote functional recovery of the nervous system, as by the release of glial-derived trophic factors (such as S-100 beta) that promote cell survival and neurite growth.

Effects of chronic maternal ethanol exposure on hippocampal and striatal morphology in offspring.

Astrocytes and serotoninergic neurons play a role in central nervous system (CNS) development, probably through serotonin (5HT) stimulation of the glial 5HT(1A) receptor. Activation of 5HT(1A) receptors causes the release of S-100 beta, a glial derived growth factor. In vitro, astrocytes are profoundly altered by chronic maternal ethanol exposure (CMEE). CMEE is also associated with reduced 5HT brain levels and abnormal development of the serotoninergic system. In the present study we analyzed the hippocampal and striatal serotoninergic innervation and astroglial cells in the offspring of CMEE mothers. Female Wistar rats were orally exposed to ethanol 6.6% (v/v) ad libitum for 6 weeks before breeding and during gestation. After parturition, rat mothers continued receiving ethanol until pups reached 21 days old. The control group received water ad libitum. Rat offspring brains were processed by immunocytochemistry using antibodies directed to GFAP, serotonin transporter (5HTT), or S-100 beta protein. Hippocampus and striatum were studied by computer-assisted image analysis. Cell area of GFAP(+) astrocytes, surface of 5HTT(+) fibers per area unit, and relative optical density (ROD) of S-100 beta(+) astrocytes were measured and statistically processed. Our results show that astroglial GFAP was increased (astrocytes were hypertrophied) and 5HTT(+) fibers were increased in both the hippocampal CA-1 area and the striatum. On the other hand, S-100 beta ROD was increased only in the hippocampal CA-1 area but not in the striatum. The different response of the studied regions is an interesting result considering evidence of a close 5HT/astroglial relation during CNS development. These differences could be due to different gradients of development in the studied areas and/or different responses of those areas to the effect of maternal ethanol exposure since the first stages of embryonic development.

IGF‐I and microglia/macrophage proliferation in the ischemic mouse brain

We have used a model of hypoxic-ischemic brain injury in adult male C57BL/6 mice to study insulin-like growth factor-I (IGF-I) and IGF-binding protein (IGFBP) expression in response to cerebral hypoxia-ischemia (H/I) in the adult mouse. A period of 20 min of H/I that resulted in histopathology in cortex, striatum, and thalamus was correlated with induction of mRNA for IGF-I, IGFBP-2, IGFBP-3, IGFBP-5, and glial fibrillary acidic protein (GFAP) by 4 days of recovery. Increased IGF-I mRNA was located within damaged regions and was surrounded by IGFBP-2 mRNA expression. The results of combined immunostaining/in situ hybridzation showed that the cells expressing IGFBP-2 mRNA were also GFAP-positive and comprised a subset of activated astrocytes immediately surrounding areas of damage. In contrast, staining within damaged regions showed high numbers of cells immunopositive for F4/80 and lectin B(4) indicative of microglia and macrophages but no cells immunopositive for the astrocytic proteins GFAP or S-100beta. Microglia/macrophages within the damaged areas expressed IGF-I mRNA and were also immunopositive for the proliferating cell nuclear antigen. To determine whether expression of IGF-I could contribute to proliferation of microglia, we treated purified cultures of adult brain microglia with IGF-I in the presence of (3)H-thymidine. IGF-I stimulated a twofold increase in DNA synthesis in cultures of adult brain microglia. Taken together with previous data demonstrating that IGF-I promotes proliferation of peripheral macrophages, these data support the hypothesis that IGF-I is an autocrine/paracrine mitogen for microglia/macrophages after H/I.

Circulating S100beta protein is increased in intrauterine growth-retarded fetuses.

To determine whether S100beta, an acidic calcium-binding protein previously demonstrated as a reliable indicator of a brain lesion, could be helpful in the detection of brain distress in intrauterine growth-retarded (IUGR) fetuses, we studied, by a case-control study, the correlation between S100B protein and the degree of fetoplacental blood flow impairment. Maternal and umbilical blood samples and placental tissue specimens were collected at delivery from IUGR pregnancies with normal (n = 10) or abnormal (n = 10) umbilical artery Doppler findings and from 40 uncomplicated pregnancies. S100beta protein levels were measured by means of a specific RIA, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. Overall mean S100beta proteins in umbilical plasma levels were higher (p < 0.05) in IUGR patients (121.8 +/- 70.4 fmol/mL) than in control patients (54.7 +/- 21.9 fmol/mL). IUGR fetuses with redistribution of blood flow showed the higher concentration of the protein (163.7 +/- 55.2 fmol/mL). Fetal S100beta concentrations correlated with middle cerebral artery pulsatility index (r = -0.536, p < 0.03) and with umbilical artery pulsatility index to middle cerebral artery pulsatility index ratio (r = 0.469, p < 0.03). No difference in the localization or intensity of S100beta staining in the placental tissues or cord between uncomplicated and IUGR pregnancies was found. This study provides evidence that circulating S100beta protein is increased in IUGR fetuses and correlates with cerebral hemodynamics, suggesting that it may represent an index of cerebral cell damage in the perinatal period.

HTLV-I-associated myelopathy: are ferritin, S100beta protein, or guanine nucleotides CSF markers of disease?

In southern Brazil, there is an endemic high prevalence foci of HTLV-I and HTLV-II infection. HTLV-infected individuals may develop HAM/TSP. Little is known about HAM/TSP pathogenesis and there is a lack of disease progression markers. This study investigated ferritin, S-100beta protein, and guanine nucleotides (GN) concentrations in the CSF of 18 patients with HAM/TSP. In HAM/TSP patients, concentrations of ferritin and S100beta were increased, whereas GMP was reduced. CSF ferritin, S100beta, and GN are potential markers for HAM/TSP.

Changes in serum S100beta protein and Mini-Mental State Examination after cold (28oC) and warm (34oC) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat)

The effect of cardiopulmonary bypass temperature and blood gas management on the brain is still controversial. This study was designed to compare the changes in S100beta protein concentration and Mini-Mental State Examination in patients undergoing cold (28 degrees C) vs. warm (34 degrees C) cardiopulmonary bypass using different blood gas strategies (alpha-stat and pH-stat). Sixty patients were randomly allocated to one of four equal groups (cold alpha-stat, cold pH-stat, warm alpha-stat, warm pH-stat). Serum S100beta concentrations were measured before CPB, directly after CPB, at 4.5 h and at 24 h after CPB. Mini-Mental State Examination was performed one day before surgery and on day five after the operation. Antegrade warm blood cardioplegia (37 degrees C) was used in all patients. There was no significant difference in postoperative S100beta protein levels between the four groups. Also, there was no interaction between bypass temperature and type of blood gas strategy on S100beta levels after bypass (directly after bypass, 4.5 h and 24 h after bypass). Mini-Mental State Examination score was not affected by blood gas strategy but it was significantly lower in patients undergoing cold cardiopulmonary bypass surgery: median (range), 26 (12-29) vs. 27 (23-30) in warm patients, P = 0.014. There was no significant correlation between Mini-Mental State Examination score 5 days after CPB and S100beta levels at any of the studied time-points after CPB. These results support the use of warm CPB (34 degrees C) in patients undergoing coronary artery bypass surgery regardless of the type of blood gas strategy.

Repeated mild injury causes cumulative damage to hippocampal cells.

An interesting hypothesis in the study of neurotrauma is that repeated traumatic brain injury may result in cumulative damage to cells of the brain. However, post-injury sequelae are difficult to address at the cellular level in vivo. Therefore, it is necessary to complement these studies with experiments conducted in vitro. In this report, the effects of single and repeated traumatic injury in vitro were investigated in cultured mouse hippocampal cells using a well characterized model of stretch-induced injury. Cell damage was assessed by the level of propidium iodide (PrI) uptake and retention of fluorescein diacetate (FDA). Uninjured control wells displayed minimal PrI uptake and high levels of FDA retention. Mild, moderate and severe levels of stretch caused increasing amounts of PrI uptake, respectively, when measured at 15 min and 24 h post-injury, indicating increased cellular damage with increasing amounts of stretch. For repeated injury studies, cultures received a second injury 1 h after the initial insult. Repeated mild injury caused a slight increase in PrI uptake compared with single injury at 15 min and 24 h post-injury, which was evident primarily in glial cells. However, the neurites of neurones in cultures that received repeated insults showed signs of damage that were not evident after a single mild injury. The release of neurone-specific enolase (NSE) and S-100beta protein, two common clinical markers of CNS damage, was also measured following the repeated injuries paradigm. When measured at 6 h post-injury, both NSE and S-100beta were found to be elevated after repeated mild injuries when compared with the single injury group. These results suggest that cells of the hippocampus may be susceptible to cumulative damage following repeated mild traumatic insults. Both glial cells and neurones appear to exhibit increased signs of damage after repetitive injury. To our knowledge, this study represents the first report on the effects of repeated mechanical insults on specific cells of the brain using an in vitro model system. The biochemical pathways of cellular degradation following repeated mild injuries may differ considerably from those that are activated by a single mild insult. Therefore, we hope to use this model in order to investigate secondary pathways of cellular damage after repeated mild traumatic injury, and as a rapid and economical means of screening possibilities for treatment strategies, including pharmaceutical intervention.

Serum S100 beta Protein as a Marker of Cerebral Damage during Cardiopulmonary Bypass

Background: S100 protein has been reported to be an early marker of brain injury. It is released from the glial cell and Schwann cell specifically after brain injury, and it,s serum concentration correlates with the severity of injury. The aim of this study was to measure the serum concentration of S100 protein during cardiac surgery and to reveal the correlation between cerebral oxygenation and S100 protein. Methods: Eighteen patients undergoing cardiac surgery using cardiopulmonary bypass (CPB) were enrolled in this study. After induction of general anesthesia, the arterial-jugular venous oxygen difference (AjD), regional cerebral oxygen saturation (rS) and lactate oxygen index (LOI) were measured. They were measured after induction (T0), during CPB (T1) and at the end of CPB (T2). Serum S100 protein was measured at T0, T2, T3 (5 hours after CPB), and T4 (24 hours after CPB) using an immunoluminometric assay. We observed correlations between rS, AjD, LOI and the S100 protein concentration. Results: Serum concentrations of S100 protein were 0.18 0.20, 5.72 4.25, 1.06 1.38 and 0.58 0.44 (/L) at T0, T2, T3 and T4 respectively (normal value 0.5/L). The duration of CPB correlated with the S100 protein concentration at T2, T3 and T4 (P = 0.028, r = 0.518; P = 0.016, r = 0.557; P = 0.026, r = 0.522). There was a significant correlation between the rS at T1 and S100 protein concentration at T2, T3, and T4 (P = 0.004, r = -0.643; P = 0.006, r = -0.620; P = 0.001, r = -0.724). A correlation between AjD, LOI and S100 protein was not proven. Conclusions: Our results show that serum concentrations of S100 protein correlates with the duration of CPB and rS during CPB. S100 protein can be considered an early marker of cerebral injury after CPB, but further studies are needed for it's correlation with severity of injury.

Glial cells as a target for the development of new therapies for treating Parkinson's disease

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. This disease is mainly characterized by tremor, bradykinesia, rigidity and postural instability that results primarily from a loss of dopaminergic neurons of the nigrostriatal pathway. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is well known to damage the nigrostriatal dopaminergic pathway, as seen in Parkinson's disease. Recent evidence shows that glial-related response plays a key role in the MPTP neurotoxic process, and the blockade of glial activation may be a new therapeutic approach to treating Parkinson's disease. In view of these new insights, this article suggests that the overexpression of S100beta protein secreted by glial cells may be an exacerbating factor in the neurodegeneration of dopaminergic cells in MPTP-treated animals. (c) 2002 Prous Science. All rights reserved.

Increased serum S100beta protein concentrations following severe head injury in humans: a biochemical marker of brain death?

This study investigated S100beta protein as a biochemical serum marker of brain damage in severe head injury and brain death victims. Blood samples obtained from 15 patients with severe head injury admitted to the trauma intensive care unit (ICU), five patients with a diagnosis of brain death due to hemorrhage following cerebral aneurysm rupture, and five healthy individuals were investigated. The S100beta protein serum concentrations were analyzed with a immunoradiometric assay kit. The 15 patients with severe head injury were followed up for 6 months. Outcome was considered either death or recovery with ICU discharge. S100beta concentrations were closely related to brain damage. Among the severe head injury victims, higher S100beta concentrations were detected in those patients that progressed to death. The individuals with brain death had similar mean S100beta concentrations, irrespective of its cause (either trauma or vascular rupture). S100beta protein is a promising serum outcome predictor for severe head injury victims and may contribute to the early diagnosis of brain death.

Therapeutic effects of sodium butyrate on glioma cells in vitro and in the rat C6 glioma model.

Preliminary in vitro studies have indicated that sodium butyrate inhibits the proliferation of cultured glioma cells and induces cellular differentiation, making it potentially useful as a therapeutic agent for patients with glioblastoma multiforme. The purpose of this study was to expand on the preliminary research by investigating the effects of sodium butyrate on multiple cell lines, explanted cells from glioblastoma tumor specimens, and in vivo in the rat C6 glioma brain tumor model. Four malignant glioma cell lines (A-172, T98G, U118MG, and C6) and two primary cell cultures derived from human glioblastoma tumor specimens were treated with 2 mmol/L sodium butyrate for up to 72 hours. Sodium butyrate-induced effects on cell morphology, proliferation, cell cycle distribution, migration, glial fibrillary acidic protein staining, and S100beta protein content were determined. For in vivo studies, a total of 64 male Wistar-Furth rats underwent operations to implant C6 glioma cells stereotactically or were used as controls. The rats were treated with escalating doses of sodium butyrate by microinfusion with Alzet minipumps (Durect Corp., Cupertino, CA). Sodium butyrate treatment in vitro produced changes in morphology and glial fibrillary acidic protein expression indicative of cellular differentiation. In cell lines and explanted cells, sodium butyrate consistently inhibited glioblastoma cell proliferation (to 51 +/- 6% that of controls) and migration (to 46 +/- 17%). Intratumoral infusion of 40 mmol/L sodium butyrate prolonged the survival of Wistar-Furth rats with intracerebral C6 tumors (P = 0.013) without detectable toxicity. These data support further consideration of direct interstitial infusion of sodium butyrate in a Phase I clinical study for patients with recurrent glioblastoma multiforme.

Calcium-dependent regulation of interactions of caldesmon with calcium-binding proteins found in growth cones of chick forebrain neurons.

1. This study was undertaken to determine if caldesmon, calmodulin, S100beta, and neurocalcin delta were present in chick forebrain neurons, and if so, to investigate the interactions of these proteins in the presence of different concentrations of calcium. 2. Immunocytochemistry was used to determine the presence and localization of these proteins in cultured forebrain neurons. Western blotting, gel electrophoresis in the presence of different concentrations of calcium, chemical cross-linking, and affinity chromatography were used to investigate the interactions of these proteins with each other. 3. Our data show that caldesmon and three calcium-binding proteins (S100beta, calmodulin, and neurocalcin 3) are localized in growth cones and neurites of chick forebrain neurons in culture. In the presence of different concentration of calcium, these calcium-binding proteins have different affinities to caldesmon and to each other. S100beta binds with greater affinity than calmodulin to caldesmon, and its ability to bind to caldesmon is regulated by neurocalcin delta. 4. These findings suggest a specific calcium-dependent regulatory pathway for modulating actomyosin during growth cone motility.

The brain in Down syndrome.

Down syndrome (trisomy 21) is a genetic disease with developmental brain abnormalities resulting in early mental retardation and precocious, age dependent Alzheimer-type neurodegeneration. We tried to discuss the role of neurodevelopmental abnormalities in connection with aberrant expression of genes on chromosome 21 including amyloid precursor protein (APP), CuZn superoxide dismutase (SOD1) and glial-derived S100 beta protein for neurodegeneration in DS. In this model, alterations in developmental pathways due to aberrant gene expression can impair cellular homeostasis and predispose to neurodegeneration of certain brain regions and types of nerve cells, involving cholinergic, serotonergic and catecholaminergic transmission, by shifting balance toward a pro-apoptotic state.

Renal elimination of protein S-100 ß in pigs with acute encephalopathy

Background:

No evident neuronal damage after electroconvulsive therapy

Electroconvulsive therapy (ECT) is regarded as one of the most effective treatments for major depressive disorder but has also been associated with cognitive deficits possibly reflecting brain damage. The aim of this study was therefore to evaluate whether ECT induces cerebral damage as reflected by different biochemical measures. The concentrations in the cerebrospinal fluid (CSF) of three established markers of neuronal/glial degeneration, tau protein (tau), neurofilament (NFL) and S-100 beta protein, were determined in nine patients who fulfilled DSM-IV criteria for major depression. CSF samples were collected before and after a course of six ECT sessions. The CSF/serum (S) albumin ratio reflecting potential blood-brain barrier (BBB) dysfunction was also determined at these time points. The treatment was clinically successful with a significant decline of depressive symptoms in all patients as assessed by the Montgomery-Åsberg Rating Scale for Depression. Several patients had signs of BBB dysfunction and/or neuronal damage before the start of treatment. Levels of CSF-tau, CSF-NFL and CSF-S-100 beta levels were not significantly changed by ECT. Also the CSF/S albumin ratio was found to be unchanged after the course of ECT. In conclusion, no biochemical evidence of neuronal/glial damage or BBB dysfunction could be demonstrated following a therapeutic course of ECT.

S100-like protein in the goldfish (Carassius auratus) kidney. An immunohistochemical study.

The presence and distribution of S100-like protein in the goldfish (Carassius auratus L.) kidney has been studied by the use of immunohistochemical and histochemical methods. Simple immunohistochemistry (peroxidase anti-peroxidase method) was carried out with a polyclonal antibody against a mixture of both S100alpha and S100beta proteins. In order to confirm the cell-type containing S-100-like immunoreactivity, the colocalization of S-100-like protein immunoreactivity with periodic acid-Schiff (PAS) reaction was investigated by using double staining with indirect immunofluorescence and PAS histochemistry. S100-like immunoreactivity was detected only in juxtaglomerular cells located in the renal arterial branch and never on afferent arterioles. No immunoreactivity was observed in other tracts of the nephron or in the interstitial cells. Double staining confirmed that S-100-like immunoreactivity and PAS reactivity were colocalized in juxtaglomerular cells. These findings are the first regarding the presence and distribution of S100-like protein in the teleost kidney; they add a new member to the list of extra-neural S100-like-containing cell types and confirm that the antigen cannot be regarded as nervous-system-specific. In addition, a concentration of S100-like immunoreactivity in juxtaglomerular cells suggests the presence of S100-like calcium-binding protein-mediated activities in these cell types.

Isolation of Novel Mouse Genes Differentially Expressed in Brain Using cDNA Microarray

The major issue in the post-genome sequencing era is determination of gene expression patterns in variety of biological systems. A microarray system is a powerful technology for analyzing the expression profile of thousands of genes at one experiment. In this study, we identified highly expressed genes in mouse brain using the cDNA microarray carrying 2304 cDNAs derived from oligo-capped mouse cDNA library. Nine genes were highly expressed in adult mouse brain compared to kidney, liver, and skeletal muscle. Tissue distribution analysis by reverse transcription-coupled polymerase chain reaction (RT-PCR) revealed that consistent with the microarray data, all of the selected 9 genes were predominantly expressed in the brain. A database search showed that 5 of the 9 genes, MBP, SC1, HiAT3, S100 protein-beta, and SNAP25, were previously known to be expressed at high level in the brain and in the nervous system. One gene was highly sequenced similar to rat S-Rex-s/human NSP-C, suggesting that the gene is a mouse homologue. The remaining three genes did not match to known genes in the GenBank/EMBL database, indicating that these are novel genes highly expressed in the brain. Taken together, our cDNA microarray system can be an excellent tool for identifying differentially expressed genes in mouse brain.

Decreased S100-beta protein in schizophrenia: preliminary evidence

The S100 proteins are a family of calcium-binding proteins found in the central and peripheral nervous systems of vertebrates. S100β, the most abundant member of this family in the CNS, mediates calcium signal transduction, and shows neurotrophic, gliotrophic and mitogenic actions that influence the development and maintenance of the nervous system. Another member of the S100 family (S100A10) was found to modulate phospholipid turnover by inhibiting the activity of enzyme phospholipase A2 (PLA2). We determined the concentration of S100β protein in the plasma of 23 medicated schizophrenic patients and 23 healthy controls. S100β protein accounts for 96% of the total S100 in the brain. Schizophrenic patients showed reduced S100β concentrations ( p=0.003), and this finding was not related to clinical variables or to intake of antipsychotic medication. Decreased S100β could be related to the findings of increased PLA2 activity and to brain maldevelopment in schizophrenia. These results are discussed further with respect to the role of adenosine in S100β release.