Variations in the cerebrospinal fluid proteome following traumatic brain injury and subarachnoid hemorrhage

Connor, David E.; Chaitanya, Ganta Vijay; Chittiboina, Prashant; McCarthy, Paul; Scott, L. Keith; Schrott, Lisa M.; Minagar, Alireza; Nanda, Anil; Alexander, J. Steven

doi:10.1016/j.pathophys.2017.04.003

Cited by 27 publications

(21 citation statements)

References 225 publications

(305 reference statements)

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“…Some of the proteins were present at higher levels in the affected twin's serum ( Table 1). Many of these, including carbonic anhydrase I [11], hemoglobin subunit alpha 1 [12], alpha-2-macroglobulin [13], hyaluronan binding protein 2 [14], S100 calcium binding protein 8 [15], ficolin 3 [16], and coagulation factor II, thrombin [17] (Table 1), have previously been associated with biological pathways relevant to IS.…”

Section: Resultsmentioning

confidence: 99%

Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke

et al. 2019

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Background and Purpose: Stroke is a common disorder with significant morbidity and mortality, and complex aetiology involving both environmental and genetic risk factors. Although some of the major risk factors for stoke, such as smoking and hypertension, are welldocumented, the underlying genetic and detailed molecular mechanisms remain elusive. Exploring the relevant biochemical pathways may contribute to the clinical diagnosis of stroke and shed light on its aetiology. Methods: A comparative proteomic analysis of blood serum of a pair of monozygotic (MZ) twins discordant for ischaemic stroke (IS) was performed using a label-free quantitative proteomics approach. To overcome the limit of reproducibility in the serum preparation, two separate runs were performed, each consisting of three technical replicates per sample. Biological processes associated with proteins differentially expressed between the twins were explored with Gene Ontology (GO) classification using the functional analysis tool g:Profiler. Results: ANOVA test performed in Progenesis LC-MS identified 179 (run 1) and 209 (run 2) proteins as differentially expressed between the affected and unaffected twin (P<0.05). Furthermore, the level of serum fibulin 1, an extracellular matrix protein associated with arterial stiffness, was on average 13.37-fold higher in the affected twin. Each dataset was then analysed independently, and the proteins were classified according to GO terms. The categories overrepresented in the affected twin predominantly corresponded to stroke-relevant processes, including wound healing, blood coagulation and haemostasis, with a high proportion of the proteins overexpressed in the affected twin associated with these terms. By contrast, in the unaffected twin diagnosed with atopic dermatitis, there were increased levels of keratin proteins and GO terms associated with skin development. 3 Conclusion: The identification of cellular pathways enriched in IS as well as the up-regulation of fibulin 1 sheds new light on the underlying disease-causing mechanisms at the molecular level. Our findings of distinct proteomic signatures associated with IS and atopic dermatitis suggest proteomic profiling could be used as a general approach for improved diagnostic, prognostic and therapeutic strategies.

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Section: Resultsmentioning

confidence: 99%

Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke

et al. 2019

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“…The 16 articles selected fall into two main categories: 8 clinical papers and 8 laboratory studies on animal models of TBI [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Briefly, the 8 clinical studies identified have described four main technologies for identification of predictive biomarkers: (a) Microvescicle/Exosome, (b) MicroRNA, (c) Mass Spectroscopy, and (d) Multiplexing and Immunoassays [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Section: Resultsmentioning

confidence: 99%

Current and Future Applications of Biomedical Engineering for Proteomic Profiling: Predictive Biomarkers in Neuro-Traumatology

et al. 2018

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This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers in patients with traumatic brain injury (TBI), a critical worldwide health problem with an estimated 10 billion people affected annually worldwide. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials. Only experimental articles revolving around the management of TBI, in which the role of new devices based on innovative discoveries coming from the field of nanotechnology and biomedical engineering were highlighted, have been included and analyzed in this study. Based on theresults gathered from this research on innovative methods for genomics, epigenomics, and proteomics, their future application in this field seems promising. Despite the outstanding technical challenges of identifying reliable biosignatures for TBI and the mixed nature of studies herein described (single cells proteomics, biofilms, sensors, etc.), the clinical implementation of those discoveries will allow us to gain confidence in the use of advanced neuromonitoring modalities with a potential dramatic improvement in the management of those patients.

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“…Previous study has revealed that Prx2 is the second most protein in the CSF of traumatic brain injury and SAH patients [ 7 ]. It is not surprising that Prx2 concentration was high in CSF of SAH patients, because Prx2 is abundant in both erythrocytes and neurons [ 8 , 9 ].…”

Section: Discussionmentioning

confidence: 99%

“…Prx1-mediated activation of TLR4/NF-κB contributes to neuroinflammatory responses in intracerebral hemorrhage [ 6 ]. Recent study has demonstrated that Prx2 was the second most protein in the cerebrospinal fluid (CSF) of traumatic brain injury and SAH patients [ 7 ]. In Prxs family, Prx2 was the third abundant protein in erythrocytes and it was also highly expressed in neurons [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Peroxiredoxin 2 activates microglia by interacting with Toll-like receptor 4 after subarachnoid hemorrhage

Zhang

Zhang³

et al. 2018

J Neuroinflammation

106

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BackgroundPeroxiredoxin (Prx) protein family have been reported as important damage-associated molecular patterns (DAMPs) in ischemic stroke. Since peroxiredoxin 2 (Prx2) is the third most abundant protein in erythrocytes and the second most protein in the cerebrospinal fluid in traumatic brain injury and subarachnoid hemorrhage (SAH) patients, we assessed the role of extracellular Prx2 in the context of SAH.MethodsWe introduced a co-culture system of primary neurons and microglia. Prx2 was added to culture medium with oxyhemoglobin (OxyHb) to mimic SAH in vitro. Neuronal cell viability was assessed by lactate dehydrogenase (LDH) assay, and neuronal apoptosis was determined by TUNEL staining. Inflammatory factors in culture medium were measured by ELISA, and their mRNA levels in microglia were determined by qPCR. Toll-like receptor 4 knockout (TLR4-KO) mice were used to provide TLR4-KO microglia; ST-2825 was used to inhibit MyD88, and pyrrolidine dithiocarbamate (PDTC) was used to inhibit NF-κB. Related cellular signals were analyzed by Western blot. Furthermore, we detected the level of Prx2 in aneurysmal SAH patients’ cerebrospinal fluids (CSF) and compared its relationship with Hunt-Hess grades.ResultsPrx2 interacted with TLR4 on microglia after SAH and then activated microglia through TLR4/MyD88/NF-κB signaling pathway. Pro-inflammatory factors were expressed and released, eventually caused neuronal apoptosis. The levels of Prx2 in SAH patients positively correlated with Hunt-Hess grades.ConclusionsExtracellular Prx2 in CSF after SAH is a DAMP which resulted in microglial activation via TLR4/MyD88/NF-κB pathway and then neuronal apoptosis. Prx2 in patients’ CSF may be a potential indicator of brain injury and prognosis.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1118-4) contains supplementary material, which is available to authorized users.

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Variations in the cerebrospinal fluid proteome following traumatic brain injury and subarachnoid hemorrhage

Abstract: Consistent CSF elevation of CA-I and Prx-2 with concurrent depletion of Hp and Tf may represent a useful combination of biomarkers for the prediction of severity and prognosis following brain injury.

Cited by 27 publications

References 225 publications

Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke

Distinct proteomic profiles in monozygotic twins discordant for ischaemic stroke

Current and Future Applications of Biomedical Engineering for Proteomic Profiling: Predictive Biomarkers in Neuro-Traumatology

Peroxiredoxin 2 activates microglia by interacting with Toll-like receptor 4 after subarachnoid hemorrhage

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