The Application of Proteomics to Traumatic Brain and Spinal Cord Injuries

Sarkis, George Anis; Mangaonkar, Manasi D.; Moghieb, Ahmed; Lelling, Brian; Guertin, Michael; Yadikar, Hamad; Yang, Zhihui; Kobeissy, Firas; Wang, Kevin

doi:10.1007/s11910-017-0736-z

Cited by 23 publications

(19 citation statements)

References 80 publications

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“…Proteins already identified as having the sensitivity and specificity to be used as clinical biomarkers of TBI include S100B, neuron-specific enolase (NSE), ubiquitin C-terminal hydrolase L1 (UCH-L1), glial fibrillary acid protein (GFAP) myelin basic protein, cleaved tau protein, spectrin breakdown products (SBDPs), and NFL ( 53 , 59 – 63 ). Panels of biomarkers may be needed to provide a more accurate and complete description of the pathology ( 53 , 64 – 66 ) and could help in patients stratification, selection of treatment strategies, and outcome prediction ( 53 , 56 , 67 ). The application of combined neuroproteomics/neurosystems biology analysis in characterizing dynamic/spatial protein changes and interactions in response to injury is discussed below and cited studies are summarized in Table 2 .…”

Section: Multiplex Chemical Profilingmentioning

confidence: 99%

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Current and Emerging Technologies for Probing Molecular Signatures of Traumatic Brain Injury

et al. 2017

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Traumatic brain injury (TBI) is understood as an interplay between the initial injury, subsequent secondary injuries, and a complex host response all of which are highly heterogeneous. An understanding of the underlying biology suggests a number of windows where mechanistically inspired interventions could be targeted. Unfortunately, biologically plausible therapies have to-date failed to translate into clinical practice. While a number of stereotypical pathways are now understood to be involved, current clinical characterization is too crude for it to be possible to characterize the biological phenotype in a truly mechanistically meaningful way. In this review, we examine current and emerging technologies for fuller biochemical characterization by the simultaneous measurement of multiple, diverse biomarkers. We describe how clinically available techniques such as cerebral microdialysis can be leveraged to give mechanistic insights into TBI pathobiology and how multiplex proteomic and metabolomic techniques can give a more complete description of the underlying biology. We also describe spatially resolved label-free multiplex techniques capable of probing structural differences in chemical signatures. Finally, we touch on the bioinformatics challenges that result from the acquisition of such large amounts of chemical data in the search for a more mechanistically complete description of the TBI phenotype.

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Section: Multiplex Chemical Profilingmentioning

confidence: 99%

“…The application of combined neuroproteomics/neurosystems biology analysis in characterizing dynamic/spatial protein changes and interactions in response to injury is discussed below and cited studies are summarized in Table 2 . Excellent reviews are available for complete analysis of these aspects ( 57 , 67 , 68 ).…”

Section: Multiplex Chemical Profilingmentioning

confidence: 99%

Current and Emerging Technologies for Probing Molecular Signatures of Traumatic Brain Injury

et al. 2017

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“…Proteomic research [21, 22] using brain tissues or biofluids from either patients or animal models have made it feasible to identify a large number of proteins associated with mTBI [23,24]. MS-based proteomics possess the advantage of having no requirement of prior knowledge of the proteins being identified, allowing for unbiased, hypothesis-free biomarker discovery in complex biological samples such as plasma and brain tissue extracts.…”

Section: Introductionmentioning

confidence: 99%

Proteomic Profiling of Mouse Brains Exposed to Blast-Induced Mild Traumatic Brain Injury Reveals Changes in Axonal Proteins and Phosphorylated Tau

Chen

Song

Cui

et al. 2018

JAD

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Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by two pathological hallmarks: Tau-containing neurofibrillary tangles and amyloid-β protein (Aβ)-containing neuritic plaques. The goal of this study is to understand mild traumatic brain injury (mTBI)-related brain proteomic changes and tau-related biochemical adaptations that may contribute to AD-like neurodegeneration. We found that both phosphorylated tau (p-tau) and the ratio of p-tau/tau were significantly increased in brains of mice collected at 3 and 24 h after exposure to 82-kPa low-intensity open-field blast. Neurological deficits were observed in animals at 24 h and 7 days after the blast using Simple Neuroassessment of Asymmetric imPairment (SNAP) test, and axon/dendrite degeneration was revealed at 7 days by silver staining. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to analyze brain tissue labeled with isobaric mass tags for relative protein quantification. The results from the proteomics and bioinformatic analysis illustrated the alterations of axonal and synaptic proteins in related pathways, including but not being limited to substantia nigra development, cortical cytoskeleton organization, and synaptic vesicle exocytosis, suggesting a potential axonal damage caused by blast-induced mTBI. Among altered proteins found in brains suffering blast, microtubule-associated protein 1B, stathmin, neurofilaments, actin binding proteins, myelin basic protein, calcium/calmodulin-dependent protein kinase, and synaptotagmin I were representative ones involved in altered pathways elicited by mTBI. Therefore, TBI induces elevated phospho-tau, a pathological feature found in brains of AD, and altered a number of neurophysiological processes, supporting the notion that blast-induced mTBI as a risk factor contributes to AD pathogenesis. LC/MS-based profiling has presented candidate target/pathways that could be explored for future therapeutic development.

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“…No curative treatment yet exists for SCI, and rehabilitation is the only therapeutic option that can contribute to functional improvement in patients. Mass spectrometry proteomics has become a powerful tool in biomedical research over the past 20 years [37], including its applications for studying the differential proteome in SCI [38,39]. In this context, here, we utilized an unbiased proteomic approach with two independent but complementary techniques (iTRAQ and 2D-DIGE) to search for protein biomarkers as indicators of improvement associated with the administration of GH in patients with SCI.…”

Section: Discussionmentioning

confidence: 99%

Effects of Growth Hormone Treatment and Rehabilitation in Incomplete Chronic Traumatic Spinal Cord Injury: Insight from Proteome Analysis

Martín-Rojas

Sastre-Oliva

Esclarín-Ruz

et al. 2020

JPM

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Despite promising advances in the medical management of spinal cord injury (SCI), there is still no available effective therapy to repair the neurological damage in patients who experience this life-transforming condition. Recently, we performed a phase II/III placebo-controlled randomized trial of safety and efficacy of growth hormone (GH) treatment in incomplete chronic traumatic spinal cord injury. The main findings were that the combined treatment of GH plus rehabilitation treatment is feasible and safe, and that GH but not placebo slightly improves the SCI individual motor score. Moreover, we found that an intensive and long-lasting rehabilitation program per se increases the functional outcome of SCI individuals. To understand the possible mechanisms of the improvement due to GH treatment (motor score) and due to rehabilitation (functional outcome), we used a proteomic approach. Here, we used a multiple proteomic strategy to search for recovery biomarkers in blood plasma with the potential to predict response to somatropin treatment and to delayed intensive rehabilitation. Forty-six patients were recruited and followed for a minimum period of 1 year. Patients were classified into two groups based on their treatment: recombinant somatropin (0.4 mg) or placebo. Both groups received rehabilitation treatment. Our strategy allowed us to perform one of the deepest plasma proteomic analyses thus far, which revealed two proteomic signatures with predictive value: (i) response to recombinant somatropin treatment and (ii) response to rehabilitation. The proteins implicated in these signatures are related to homeostasis, inflammation, and coagulation functions. These findings open novel possibilities to assess and therapeutically manage patients with SCI, which could have a positive impact on their clinical response.

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The Application of Proteomics to Traumatic Brain and Spinal Cord Injuries

Cited by 23 publications

References 80 publications

Current and Emerging Technologies for Probing Molecular Signatures of Traumatic Brain Injury

Current and Emerging Technologies for Probing Molecular Signatures of Traumatic Brain Injury

Proteomic Profiling of Mouse Brains Exposed to Blast-Induced Mild Traumatic Brain Injury Reveals Changes in Axonal Proteins and Phosphorylated Tau

Effects of Growth Hormone Treatment and Rehabilitation in Incomplete Chronic Traumatic Spinal Cord Injury: Insight from Proteome Analysis

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