Journal article
Identification of chronic brain protein changes and protein targets of serum auto-antibodies after blast-mediated traumatic brain injury
Heliyon, Vol.6(2), pp.e03374-e03374
02/2020
DOI: 10.1016/j.heliyon.2020.e03374
PMCID: PMC7029173
PMID: 32099918
Abstract
In addition to needing acute emergency management, blast-mediated traumatic brain injury (TBI) is also a chronic disorder with delayed-onset symptoms that manifest and progress over time. While the immediate consequences of acute blast injuries are readily apparent, chronic sequelae are harder to recognize. Indeed, the identification of individuals with mild-TBI or TBI-induced symptoms is greatly impaired in large part due to the lack of objective and robust biomarkers. The purpose of this study was to address these need by identifying candidates for serum-based biomarkers of blast TBI, and also to identify unique or differentially regulated protein expression in the thalamus in C57BL/6J mice exposed to blast using high throughput qualitative screens of protein expression. To identify thalamic proteins differentially or uniquely associated with blast exposure, we utilized an antibody-based affinity-capture strategy (referred to as “proteomics-based analysis of depletomes”; PAD) to deplete thalamic lysates from blast-treated mice of endogenous thalamic proteins also found in control mice. Analysis of this “depletome” detected 75 unique proteins, many with associations to the myelin sheath. To identify blast-associated proteins eliciting production of circulating autoantibodies, serum antibodies of blast-treated mice were immobilized, and their immunogens subsequently identified by proteomic analysis of proteins specifically captured following incubation with thalamic lysates (a variant of a strategy referred to as “proteomics-based expression library screening”; PELS). This analysis identified 46 blast-associated immunogenic proteins, including 6 shared in common with the PAD analysis (ALDOA, PHKB, HBA-A1, DPYSL2, SYN1, and CKB). These proteins and their autoantibodies are appropriate for further consideration as biomarkers of blast-mediated TBI.
Biochemistry; Neuroscience; Proteins; Retinal ganglion cell; Biomarker; Blast injury; Traumatic brain injury.
Details
- Title: Subtitle
- Identification of chronic brain protein changes and protein targets of serum auto-antibodies after blast-mediated traumatic brain injury
- Creators
- Matthew M Harper - The Iowa City Department of Veterans Affairs Medical Center, Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, USADanielle Rudd - The Iowa City Department of Veterans Affairs Medical Center, Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, USAKacie J Meyer - The University of Iowa Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA, USAAnumantha. G Kanthasamy - Department of Biomedical Sciences, Iowa State University, Ames, IA, USAVellareddy Anantharam - PK Biosciences, Ames, IA, USAAndrew A Pieper - Harrington Discovery Institute, University Hospitals of Cleveland, Department of Psychiatry Case Western Reserve University, Geriatric Research Education and Clinical Centers, Louis Stokes VA Medical Center, Cleveland, OH 44106, USAEdwin Vázquez-Rosa - Harrington Discovery Institute, University Hospitals of Cleveland, Department of Psychiatry Case Western Reserve University, Geriatric Research Education and Clinical Centers, Louis Stokes VA Medical Center, Cleveland, OH 44106, USAMin-Kyoo Shin - Harrington Discovery Institute, University Hospitals of Cleveland, Department of Psychiatry Case Western Reserve University, Geriatric Research Education and Clinical Centers, Louis Stokes VA Medical Center, Cleveland, OH 44106, USAKalyani Chaubey - Harrington Discovery Institute, University Hospitals of Cleveland, Department of Psychiatry Case Western Reserve University, Geriatric Research Education and Clinical Centers, Louis Stokes VA Medical Center, Cleveland, OH 44106, USAYeojung Koh - Harrington Discovery Institute, University Hospitals of Cleveland, Department of Psychiatry Case Western Reserve University, Geriatric Research Education and Clinical Centers, Louis Stokes VA Medical Center, Cleveland, OH 44106, USALucy P Evans - The University of Iowa Department of Pediatrics, University of Iowa, Iowa City, IA, USAAlexander G Bassuk - The University of Iowa Department of Pediatrics, University of Iowa, Iowa City, IA, USAMichael G Anderson - The Iowa City Department of Veterans Affairs Medical Center, Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, USALaura Dutca - The Iowa City Department of Veterans Affairs Medical Center, Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, USAIndira T Kudva - Food Safety and Enteric Pathogens Research Unit, National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, IA, USAManohar John - Pathovacs, Inc., Ames, IA, USA
- Resource Type
- Journal article
- Publication Details
- Heliyon, Vol.6(2), pp.e03374-e03374
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.heliyon.2020.e03374
- PMID
- 32099918
- PMCID
- PMC7029173
- ISSN
- 2405-8440
- eISSN
- 2405-8440
- Grant note
- DOI: 10.13039/100000005, name: U.S. Department of Defense; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs
- Language
- English
- Date published
- 02/2020
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biology; Neurology (Pediatrics); Ophthalmology and Visual Sciences
- Record Identifier
- 9984070401902771
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