Document Type

Article

Original Publication Date

2014

Journal/Book/Conference Title

Journal of Neurotrauma

Volume

31

Issue

8

First Page

782

Last Page

788

DOI of Original Publication

10.1089/neu.2013.3116

Comments

Dr. Niemeier is currently at Carolinas Rehabilitation, Charlotte, North Carolina.

Date of Submission

March 2015

Abstract

Heterogeneity within brain injury presents a challenge to the development of informative molecular diagnostics. Recent studies show progress particularly in cerebrospinal fluid with biomarker assays targeting one or a few structural proteins. Protein-based assays in peripheral fluids, however, have been more challenging to develop in part due to restricted and intermittent barrier access. Further, a greater number of molecular variables may be required to inform on patient status given the multifactorial nature of brain injury. Presented is an alternative approach profiling peripheral fluid for a class of small metabolic by-products rendered by ongoing brain pathobiology. Urine specimens were collected for head trauma subjects upon admission to acute brain injury rehabilitation and nontraumatized matched controls. An innovative data-independent mass spectrometry approach was employed for reproducible molecular quantification across osmolarity-normalized samples. The postacute human traumatic brain injury urinary signature encompassed 2,476 discriminant variables reproducibly measured in specimens for subject classification. Multiple sub-profiles were then discerned in correlation with injury severity per Glasgow Comma Scale and behavioral and neurocognitive function per Patient Competency Rating Scale and Frontal Systems Behavioral Scale. Identified peptide constituents were enriched for outgrowth and guidance, extracellular matrix and post-synaptic density proteins, which were reflective of ongoing post-acute neuroplastic processes demonstrating pathobiological relevance. Taken together, these findings support further development of diagnostics based on brain injury urinary signatures using either combinatorial quantitative models or patternrecognition methods. Particularly, these findings espouse assay development to address unmet diagnostic and theragnostic needs in brain injury rehabilitative medicine.

Rights

© Mary Ann Liebert, Inc. This is the author’s version of a work that was accepted for publication in Journal of Neurotrauma. April 15, 2014, 31(8): 782-788. Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/neu.2013.3116.

Is Part Of

VCU Anatomy and Neurobiology Publications

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