Evaluation of serum Neuron‐specific enolase, S100B, myelin basic protein and glial fibrilliary acidic protein as brain specific proteins in children with autism spectrum disorder

Esnafoğlu, Erman; Ayyıldız, Sema Nur; Cırrık, Selma; Ertürk, Emine Yurdakul; Erdil, Abdullah; Dağlı, Abdullah; Noyan, Tevfik

doi:10.1016/j.ijdevneu.2017.06.011

Cited by 32 publications

(40 citation statements)

References 60 publications

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“…A study, including 40 children with autism reported not only their increased S100B concentrations, but its association with autism severity (Guloksuz et al 2017). Contrary, one study with 35 children with ASD found no difference in serum S100B with controls (Esnafoglu et al 2017). This discordance in results could be based on small groups of included children, amongst which our study was the largest.…”

Section: Discussioncontrasting

confidence: 89%

Plasma Levels of Glial Cell Marker S100B in Children With Autism

et al. 2019

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Autism spectrum disorder (ASD) is a neurodevelopmental condition with increasing incidence. Recent evidences suggest glial cells involvement in autism pathophysiology. S100B is a calcium binding protein, mainly found in astrocytes and therefore used as a marker of their activity. In our study, children with autism had higher plasma concentrations of S100B compared to non-autistic controls. No association of S100B plasma levels with behavioral symptoms (ADI-R and ADOS-2 scales) was found. Plasma S100B concentration significantly correlated with urine serotonin, suggesting their interconnection. Correlation of plasma S100B levels with stool calprotectin concentrations was found, suggesting not only brain astrocytes, but also enteric glial cells may take part in autism pathogenesis. Based on our findings, S100B seems to have a potential to be used as a biomarker of human neurodevelopmental disorders, but more investigations are needed to clarify its exact role in pathomechanism of autism.

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Section: Discussioncontrasting

confidence: 89%

Plasma Levels of Glial Cell Marker S100B in Children With Autism

et al. 2019

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“…Astrocyte‐derived membranous blebs have not been observed in other CNS disorders, and we suggest they may be generated by a targeted attack of astrocyte processes by cytotoxic T lymphocytes specifically at the glia limitans surrounding blood vessels and other CFS–brain boundaries. Consistent with our findings of increased GFAP + astrocyte debris in perivascular Virchow–Robin space CSF in ASD, GFAP is elevated in CSF and serum in a large proportion of individuals with ASD . The strong separation of ASD from control cases on a lymphocyte count versus jaggedness index scatterplot (see Fig D) and the correlation of lymphocyte count with astrocyte debris on a scatterplot of ASD cases (see Fig C) suggest these histologic features could be causally connected biomarkers of the ASD pathogenic process.…”

Section: Discussionmentioning

confidence: 61%

“…Consistent with our findings of increased GFAP + astrocyte debris in perivascular Virchow-Robin space CSF in ASD, GFAP is elevated in CSF and serum in a large proportion of individuals with ASD. 13 The strong separation of ASD from control cases on a lymphocyte count versus jaggedness index scatterplot (see Fig 5D) and the correlation of lymphocyte count with astrocyte debris on a scatterplot of ASD cases (see Fig 2C) suggest these histologic features could be causally connected biomarkers of the ASD pathogenic process. Our findings suggest future diagnostic evaluations and research of ASD postmortem brains should examine the following: (1) perivascular CD8 + T-lymphocyte infiltrates, (2) CSF-glia limitans barrier damage (including increased perivascular space and collagen deposition), and (3) GFAP + astrocyte membranous blebs in CSF space compartments.…”

Section: Discussionmentioning

confidence: 95%

T lymphocytes and cytotoxic astrocyte blebs correlate across autism brains

DiStasio

Nagakura

Nadler

et al. 2019

Annals of Neurology

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Objective Autism spectrum disorder (ASD) affects 1 in 59 children, yet except for rare genetic causes, the etiology in most ASD remains unknown. In the ASD brain, inflammatory cytokine and transcript profiling shows increased expression of genes encoding mediators of the innate immune response. We evaluated postmortem brain tissue for adaptive immune cells and immune cell–mediated cytotoxic damage that could drive this innate immune response in the ASD brain. Methods Standard neuropathology diagnostic methods including histology and immunohistochemistry were extended with automated image segmentation to quantify identified pathologic features in the postmortem brains. Results We report multifocal perivascular lymphocytic cuffs contain increased numbers of lymphocytes in ~65% of ASD compared to control brains in males and females, across all ages, in most brain regions, and in white and gray matter, and leptomeninges. CD3+ T lymphocytes predominate over CD20+ B lymphocytes and CD8+ over CD4+ T lymphocytes in ASD brains. Importantly, the perivascular cuff lymphocyte numbers correlate to the quantity of astrocyte‐derived round membranous blebs. Membranous blebs form as a cytotoxic reaction to lymphocyte attack. Consistent with multifocal immune cell–mediated injury at perivascular cerebrospinal fluid (CSF)–brain barriers, a subset of white matter vessels have increased perivascular space (with jagged contours) and collagen in ASD compared to control brains. CSF–brain barrier pathology is also evident at cerebral cortex pial and ventricular ependymal surfaces in ASD. Interpretation The findings suggest dysregulated cellular immunity damages astrocytes at foci along the CSF–brain barrier in ASD. ANN NEUROL 2019;86:885–898

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“…The evidence for whether BBB disruption is present in ASD based on molecular markers of increased BBB permeability such as S100B, GFAP, neuron-specific enolase (NSE), myelin basic protein (MBP), and creatine kinase brain isoenzyme (CK-BB) is mixed. One recent study found that S100B, GFAP, and NSE did not differ between ASD and control children but did find that GFAP levels were significantly higher in ASD individuals and GFAP levels positively correlated with scores on the Childhood Autism Rating Scale [147]. Other studies did find significantly increased levels of S100β in serum [148] and in plasma [149] for children with ASD and that this correlated with increased levels of the cytokine tumour necrosis factor-alpha (TNF-α) [149].…”

Section: Markers Of Bbb Permeability In Asdmentioning

confidence: 99%

Blood-brain barrier regulation in psychiatric disorders

Kealy

Greene

Campbell

2020

Neuroscience Letters

197

135

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The blood-brain barrier (BBB) is a dynamic interface between the peripheral blood supply and the cerebral parenchyma, controlling the transport of material to and from the brain. Tight junctions between the endothelial cells of the cerebral microvasculature limit the passage of large, negatively charged molecules via paracellular diffusion whereas transcellular transportation across the endothelial cell is controlled by a number of mechanisms including transporter proteins, endocytosis, and diffusion. Here, we review the evidence that perturbation of these processes may underlie the development of psychiatric disorders including schizophrenia, autism spectrum disorder (ASD), and affective disorders. Increased permeability of the BBB appears to be a common factor in these disorders, leading to increased infiltration of peripheral material into the brain culminating in neuroinflammation and oxidative stress. However, although there is no common mechanism underpinning BBB dysfunction even within each particular disorder, the tight junction protein claudin-5 may be a clinically relevant target given that both clinical and pre-clinical research has linked it to schizophrenia, ASD, and depression. Additionally, we discuss the clinical significance of the BBB in diagnosis (genetic markers, dynamic contrast-enhanced-magnetic resonance imaging, and blood biomarkers) and in treatment (drug delivery).

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Evaluation of serum Neuron‐specific enolase, S100B, myelin basic protein and glial fibrilliary acidic protein as brain specific proteins in children with autism spectrum disorder

Abstract: While serum NSE, MBP, and S100B values cannot be considered as biomarkers for ASD, GFAP may be a biomarker and is suggested as a possible indicator of autism severity.

Cited by 32 publications

References 60 publications

Plasma Levels of Glial Cell Marker S100B in Children With Autism

Plasma Levels of Glial Cell Marker S100B in Children With Autism

T lymphocytes and cytotoxic astrocyte blebs correlate across autism brains

Blood-brain barrier regulation in psychiatric disorders

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