Time-Dependent Changes in Serum Level of Protein Biomarkers after Focal Traumatic Brain Injury

Rostami, Elham

doi:10.4172/2376-0281.1000168

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…Plasma levels of ceruloplasmin, neurofilament heavy chain (NF-H), tau protein, vascular endothelial growth factor (VEGF), 4-hydroxynonenal Michael adducts (4-HNE), neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), and S100 calcium binding protein β subunit (S100β) were assayed using reverse phase protein microarray (RPPM). Sample preparation, printing, scanning, and data analysis for RPPM were performed as described previously 19 20 21 22 23 37 38 39 40 . Frozen plasma samples were thawed on ice and diluted 1:10 with Dilution Buffer (3 parts Lysis Buffer [TPER, 10% Glycerol, 1× HALT] and 1 part 4× SDS Sample Buffer [35% Glycerol, 0.8% SDS, 10× TBS, 10× TCEP, 1× HALT, 0.0035% NaN 3 ]).…”

Section: Methodsmentioning

confidence: 99%

Behavioral, blood and magnetic resonance imaging biomarkers of experimental mild traumatic brain injury

Wright

Trezise

Kamnaksh

et al. 2016

Sci Rep

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Repeated mild traumatic brain injuries (mTBI) may lead to serious neurological consequences, especially if re-injury occurs within the period of increased cerebral vulnerability (ICV) triggered by the initial insult. MRI and blood proteomics might provide objective measures of pathophysiological changes in mTBI, and indicate when the brain is no longer in a state of ICV. This study assessed behavioral, MRI, and blood-based markers in a rat model of mTBI. Rats were given a sham or mild fluid percussion injury (mFPI), and behavioral testing, MRI, and blood collections were conducted up to 30 days post-injury. There were cognitive impairments for three days post-mFPI, before normalizing by day 5 post-injury. In contrast, advanced MRI (i.e., tractography) and blood proteomics (i.e., vascular endothelial growth factor) detected a number of abnormalities, some of which were still present 30 days post-mFPI. These findings suggest that MRI and blood proteomics are sensitive measures of the molecular and subtle structural changes following mTBI. Of particular significance, this study identified novel tractography measures that are able to detect mTBI and may be more sensitive than traditional diffusion-tensor measures. Furthermore, the blood and MRI findings may have important implications in understanding ICV and are translatable to the clinical setting.

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Section: Methodsmentioning

confidence: 99%

Behavioral, blood and magnetic resonance imaging biomarkers of experimental mild traumatic brain injury

Wright

Trezise

Kamnaksh

et al. 2016

Sci Rep

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“…As discussed above, the acute phase of TBI is dominated by the consequences of the primary injury, and changes in protein biomarker levels in CSF and/or serum can reflect the underlying pathologies. Neuron-and glia-specific proteins such as UCHL1, GFAP, and NSE are released from damaged and dying cells and their levels peak in biofluids at the earliest measured time point (Agoston and Kamnaksh, 2015;Diaz-Arrastia et al, 2014;Rostami et al, 2015;Wang et al, 2018). Similarly, axonal damage is reflected in the peak levels of p-tau and NF proteins (Rubenstein et al, 2017;Wang et al, 2016a).…”

Section: The Time Factormentioning

confidence: 99%

Protein biomarkers of epileptogenicity after traumatic brain injury

Agoston

Kamnaksh

2019

Neurobiology of Disease

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Traumatic brain injury (TBI) is a major risk factor for acquired epilepsy. Post-traumatic epilepsy (PTE) develops over time in up to 50% of patients with severe TBI. PTE is mostly unresponsive to traditional anti-seizure treatments suggesting distinct, injury-induced pathomechanisms in the development of this condition. Moderate and severe TBIs cause significant tissue damage, bleeding, neuron and glia death, as well as axonal, vascular, and metabolic abnormalities. These changes trigger a complex biological response aimed at curtailing the physical damage and restoring homeostasis and functionality. Although a positive correlation exists between the type and severity of TBI and PTE, there is only an incomplete understanding of the time-dependent sequelae of TBI pathobiologies and their role in epileptogenesis. Determining the temporal profile of protein biomarkers in the blood (serum or plasma) and cerebrospinal fluid (CSF) can help to identify pathobiologies underlying the development of PTE, high-risk individuals, and disease modifying therapies. Here we review the pathobiological sequelae of TBI in the context of blood- and CSF-based protein biomarkers, their potential role in epileptogenesis, and discuss future directions aimed at improving the diagnosis and treatment of PTE.

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“…Understanding the temporal aspect of the various pathobiological changes is important for physicians to make an informed decision about the need, type and, importantly, the timing of medical intervention. Biofluid-based protein biomarkers in TBI could assist, complement, and enhance the information content obtained from current, routinely used imaging, physiological and neurobehavioral/functional outcome measures [44,65,86,93,99,100]. They should accurately distinguish disturbance from damage, provide molecular-level information of the extent of damage and the pathobiological The pathobiological responses can, at least partially, overlap and interact with one another [65,[96][97][98].…”

Section: Introductionmentioning

confidence: 99%

Fluid-Based Protein Biomarkers in Traumatic Brain Injury: The View from the Bedside

Agoston,

Helmy

2023

IJMS

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There has been an explosion of research into biofluid (blood, cerebrospinal fluid, CSF)-based protein biomarkers in traumatic brain injury (TBI) over the past decade. The availability of very large datasets, such as CENTRE-TBI and TRACK-TBI, allows for correlation of blood- and CSF-based molecular (protein), radiological (structural) and clinical (physiological) marker data to adverse clinical outcomes. The quality of a given biomarker has often been framed in relation to the predictive power on the outcome quantified from the area under the Receiver Operating Characteristic (ROC) curve. However, this does not in itself provide clinical utility but reflects a statistical association in any given population between one or more variables and clinical outcome. It is not currently established how to incorporate and integrate biofluid-based biomarker data into patient management because there is no standardized role for such data in clinical decision making. We review the current status of biomarker research and discuss how we can integrate existing markers into current clinical practice and what additional biomarkers do we need to improve diagnoses and to guide therapy and to assess treatment efficacy. Furthermore, we argue for employing machine learning (ML) capabilities to integrate the protein biomarker data with other established, routinely used clinical diagnostic tools, to provide the clinician with actionable information to guide medical intervention.

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Time-Dependent Changes in Serum Level of Protein Biomarkers after Focal Traumatic Brain Injury

Cited by 6 publications

References 41 publications

Behavioral, blood and magnetic resonance imaging biomarkers of experimental mild traumatic brain injury

Behavioral, blood and magnetic resonance imaging biomarkers of experimental mild traumatic brain injury

Protein biomarkers of epileptogenicity after traumatic brain injury

Fluid-Based Protein Biomarkers in Traumatic Brain Injury: The View from the Bedside

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