Identification of <b><i>post‐mortem</i></b> cerebrospinal fluid proteins as potential biomarkers of ischemia and neurodegeneration

Lescuyer, Pierre; Allard, Laure; Zimmermann‐Ivol, Catherine G.; Burgess, Jennifer A.; Hughes-Frutiger, Séverine; Burkhard, Pierre; Sanchez, Jean‐Charles; Hochstrasser, Denis F.

doi:10.1002/pmic.200300822

Cited by 93 publications

(82 citation statements)

References 73 publications

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“…Given that novel, potentially neurodestructive proteins can be detected in the CSF 6 h after brain death (Lescuyer et al, 2004), we addressed the possibility that the CSF from our NP-SLE patient became neurotoxic within 3-4 h post mortem. For this purpose we included the CSF sample from a 27-year old drug addict who died from a drug overdose and was subjected for autopsy at a time comparable to the NP-SLE patient.…”

Section: Human Tissuesmentioning

confidence: 99%

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

Šakić

Kirkham

Ballok

et al. 2005

Journal of Neuroimmunology

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Brain atrophy, neurologic and psychiatric (NP) manifestations are common complications in the systemic autoimmune disease, lupus erythematosus (SLE). Here we show that the cerebrospinal fluid (CSF) from autoimmune MRL-lpr mice and a deceased NP-SLE patient reduce the viability of brain cells which proliferate in vitro. This detrimental effect was accompanied by periventricular neurodegeneration in the brains of autoimmune mice and profound in vivo neurotoxicity when their CSF was administered to the CNS of a rat. Multiple ionic responses with microfluorometry and protein peaks on electropherograms suggest more than one mechanism of cellular demise. Similar to the CSF from diseased MRL-lpr mice, the CSF from a deceased SLE patient with a history of psychosis, memory impairment, and seizures, reduced viability of the C17.2 neural stem cell line. Proposed mechanisms of cytotoxicity involve binding of intrathecally synthesized IgG autoantibodies to target(s) common to different mammalian species and neuronal populations. More importantly, these results indicate that the viability of proliferative neural cells can be compromised in systemic autoimmune disease. Antibody-mediated lesions of germinal layers may impair the regenerative capacity of the brain in NP-SLE and possibly, brain development and function in some forms of CNS disorders in which autoimmune phenomena have been documented. AbbreviationsACA, anti-cardiolipin antibodiesx; Abbreviations, anti-nuclear antibodies; CSF, cerebrospinal fluid; FJB, Fluoro Jade B stain; NP-SLE, neuropsychiatric systemic lupus erythematosus; PBS, phosphate buffered saline

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Section: Human Tissuesmentioning

confidence: 99%

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

Šakić

Kirkham

Ballok

et al. 2005

Journal of Neuroimmunology

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“…This could include analysis of neighboring fluids of a particular organ or tissue (e.g. CSF for markers of brain damage 31,32 ). When carried on plasma or urine, the proteomic analysis should involve a fractionation step aiming at the selection of a subclass of proteins to carry out the biomarker search.…”

Section: A Relevant Questionmentioning

confidence: 99%

How Shall We Use the Proteomics Toolbox for Biomarker Discovery?

2007

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Biomarker discovery for clinical purposes is one of the major areas in which proteomics is used. However, despite considerable effort, the successes have been relatively scarce. In this perspective paper, we try to figure out and analyze the main causes for this limited success, and to suggest alternate strategies, which will avoid them, without eluding the foreseeable weak points of these strategies. Two major strategies are analyzed, namely the switch from body fluids to cell and tissues for the initial biomarker discovery step or, if body fluids must be analyzed, the implementation of highly selective protein selection strategies.Keywords : proteomics ; biomarkers ; plasma ; biological fluids ; cerebrospinal fluid ; Synopsis : this paper aims at stimulating discussions on how proteomics could be best used for

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“…Such postmortem changes in CSF protein may result from cell death, breakdown of the blood-brain barrier, or other events that are initiated when an individual dies. It has been proposed that a comparison of antemortem and postmortem CSF protein production may yield biomarkers for some neurological disorders (2 ). Accordingly, several studies used enzyme activity assays to measure postmortem changes in human CSF proteins such as lactate dehydrogenase, ␤-glucuronidase, and acid phosphatase (3,4 ).…”

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confidence: 99%

Proteomic Analysis of Cerebrospinal Fluid Changes Related to Postmortem Interval

et al. 2006

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Background:The study of proteins with altered production in postmortem cerebrospinal fluid (CSF) compared with antemortem CSF may improve the understanding of biochemical changes that occur immediately after death. Methods: Two CSF samples (1 antemortem and 1 postmortem) were collected from 7 patients and analyzed by 2-dimensional gel electrophoresis. An analysis was also performed to identify proteins that showed a correlation between concentration change and postmortem interval. Tandem mass spectrometry was used to identify the proteins. Results: Fifty-four protein spots were identified that showed a consistent and significant change in concentration in the postmortem CSF of all 7 patients (>3.5-fold, P <0.01). The proteins in these spots derive from a variety of functional groups, including cytoskeletal proteins, enzymes involved in glycolysis, and proteins that prevent oxidative stress. Fourteen protein spots were found to have an increase in production that correlated with postmortem interval. Conclusions: Changes in protein production of postmortem vs antemortem CSF were studied. The proteins observed to change production in the postmortem CSF include several proteins previously observed as potential stroke biomarkers.

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Identification of post‐mortem cerebrospinal fluid proteins as potential biomarkers of ischemia and neurodegeneration

Cited by 93 publications

References 73 publications

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

Proliferating brain cells are a target of neurotoxic CSF in systemic autoimmune disease

How Shall We Use the Proteomics Toolbox for Biomarker Discovery?

Proteomic Analysis of Cerebrospinal Fluid Changes Related to Postmortem Interval

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