Trial reportThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Serum transthyretin monomer as a possible marker of blood-to-CSF barrier disruption.
Trial report in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 4 syntheses or guidelines pooled it, 96 citations in OpenAlex.
- Therapeutic modulation of the blood-brain barrier in brain tumors: a systematic review of clinical and translational approaches.Cancer chemotherapy and pharmacology · 2026Pooled it
- Peripheral Blood and Salivary Biomarkers of Blood-Brain Barrier Permeability and Neuronal Damage: Clinical and Applied Concepts.Frontiers in neurology · 2020Pooled it
- Proteomic analysis of cerebrospinal fluid: toward the identification of biomarkers for gliomas.Neurosurgical review · 2014Pooled it
- A systematic review of the biomarker S100B: implications for sport-related concussion management.Journal of athletic trainingPooled it
- Trial
- Review
- Altered levels of transthyretin in human cerebral microdialysate after subarachnoid haemorrhage using proteomics; a descriptive pilot study.Proteome science · 2023Article
- S100B, Actor and Biomarker of Mild Traumatic Brain Injury.International journal of molecular sciences · 2023Review
- Article
- Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment.Theranostics · 2022Review
- A Haptoglobin Exon Copy Number Variant Associates With HIV-Associated Neurocognitive Impairment in European and African-Descent Populations.Frontiers in genetics · 2021Article
- A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity.Fluids and barriers of the CNS · 2020Review
- Metabolomic Profiling in Neuromyelitis Optica Spectrum Disorder Biomarker Discovery.Metabolites · 2020Review
- Influence of Blood-Brain Barrier Integrity on Brain Protein Biomarker Clearance in Severe Traumatic Brain Injury: A Longitudinal Prospective Study.Journal of neurotrauma · 2020Observational
- Serum Visinin-Like Protein 1 Is a Better Biomarker Than Neuron-Specific Enolase for Seizure-Induced Neuronal Injury: A Prospective and Observational Study.Frontiers in neurology · 2020Article
- Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases.International journal of molecular sciences · 2019Review
- A review of the clinical utility of serum S100B protein levels in the assessment of traumatic brain injury.Acta neurochirurgica · 2017Review
- Improving the clinical management of traumatic brain injury through the pharmacokinetic modeling of peripheral blood biomarkers.Fluids and barriers of the CNS · 2016Article
- S100B blood levels and childhood trauma in adolescent inpatients.Journal of psychiatric research · 2015Article
- Does Systemic Inflammation Play a Role in Pediatric Psychosis?Clinical schizophrenia & related psychoses · 2015Article
Corrections and comments
- Erratum issuedVolgelbaum, M [corrected to Vogelbaum, M]
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The CNS is shielded from systemic influences by two separate barriers, the blood-brain barrier (BBB) and the blood-to-CSF barrier. Failure of either barrier bears profound significance in the etiology and diagnosis of several neurological diseases. Furthermore, selective opening of BBB tight junctions provides an opportunity for delivery of otherwise BBB impermeant drugs. Peripheral assessment of BBB opening can be achieved by detection in blood of brain-specific proteins that extravasate when these endothelial junctions are breached. We developed a proteomic approach to discover clusters of CNS-specific proteins with extravasation into serum that correlates with BBB openings. Protein profiles from blood samples obtained from patients undergoing iatrogenic BBB disruption (BBBD) with intra-arterial hyperosmotic mannitol were compared with pre-BBB opening serum. A low molecular weight protein (14 kDa) identified by mass spectroscopy as transthyretin (TTR) consistently correlated with BBBD. Protein gel electrophoresis and immunodetection confirmed that TTR was indeed extravasated in its monomeric form when CNS barriers were breached. The time course of TTR extravasation was compared with release from the brain of another BBB integrity marker, S-100beta (11 kDa). Kinetic analysis revealed that the appearance of S-100beta, presumably originating from perivascular astrocytic end feet, preceded extravasation of TTR by several minutes. Because TTR is localized primarily in choroid plexus and, as a soluble monomer, in CSF, we concluded that although S-100beta is a marker of BBB integrity, TTR instead may be a peripheral tracer of blood-to-cerebrospinal barrier.
Indexed as
Identifiers
12629200PMC6741971W2151291785What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.