Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue

Sami Abu Hamdeh,Niklas Marklund,Ganna Shevchenko,Sravani Musunuri,Jia Mi,Jonas Bergquist

doi:10.1038/s41598-018-25060-0

Abstract

The early molecular response to severe traumatic brain injury (TBI) was evaluated using biopsies of structurally normal-appearing cortex, obtained at location for intracranial pressure (ICP) monitoring, from 16 severe TBI patients. Mass spectrometry (MS; label free and stable isotope dimethyl labeling) quantitation proteomics showed a strikingly different molecular pattern in TBI in comparison to cortical biopsies from 11 idiopathic normal pressure hydrocephalus patients. Diffuse TBI showed increased expression of peptides related to neurodegeneration (Tau and Fascin, p < 0.05), reduced expression related to antioxidant defense (Glutathione S-transferase Mu 3, Peroxiredoxin-6, Thioredoxin-dependent peroxide reductase; p < 0.05) and increased expression of potential biomarkers (e.g. Neurogranin, Fatty acid-binding protein, heart p < 0.05) compared to focal TBI. Proteomics of human brain biopsies displayed considerable molecular heterogeneity among the different TBI subtypes with consequences for the pathophysiology and development of targeted treatments for TBI.

Highlights

Traumatic brain injury is a global health problem and a leading cause of death and severe disability1,2
In the first analysis (Study A), the objective was to analyse whether molecular differences existed in structurally normal-appearing cortex between traumatic brain injury (TBI) and idiopathic normal pressure hydrocephalus (iNPH) and six TBI patient with combined diffuse and focal TBI were compared to six iNPH patients for proteome differences
The proteome profile in structurally normal-appearing cortical tissue of severe TBI patients compared to cortical tissue from patients with iNPH was analyzed using quantitative MS-based proteomics

Summary

Introduction

Traumatic brain injury is a global health problem and a leading cause of death and severe disability. TBI is commonly categorized into either focal injury that includes subdural, epidural and intracranial hemorrhages, or diffuse injury with widespread damage to axons. Mass-spectrometry (MS)-based proteomics were used on fresh brain biopsies of structurally normal-appearing frontal cortex, obtained in conjunction with the insertion of an intracranial pressure monitor acutely in 16 severe TBI patients. The aim of the study was to investigate potential differences in protein expression in focal and diffuse injury in the acute phase after TBI. Our findings show that DAI initiates unique biological pathways in comparison to focal TBI, with regulatory differences in proteins involved in energy metabolism, cytoskeletal functions, and mechanisms of oxidative stress as well as differences in the regulation of proteins suggested to have important roles in the development of neurodegenerative diseases

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