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

David K Wright,Bridgette D Semple,Terence J O’Brien,Peter Stanwell,Denes V Agoston,Andrew J Gardner,Leigh A Johnston,Jack Trezise,Alaa Kamnaksh,Ramsey Bekdash,Sandy R Shultz,Roger Ordidge

doi:10.1038/srep28713

Abstract

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.

Highlights

Repeated mild traumatic brain injuries may lead to serious neurological consequences, especially if re-injury occurs within the period of increased cerebral vulnerability (ICV) triggered by the initial insult
All three of the biomarker platforms assessed were able to detect abnormalities after experimental mild traumatic brain injury (mTBI), our findings suggest that advanced Magnetic resonance imaging (MRI) and blood-based proteomics are more sensitive in identifying the duration of mTBI-induced molecular and fine structural changes than the behavioural measures examined in this study
This study investigated the use of MRI, blood proteomics, and behavioral methods as markers to detect changes and estimate recovery after experimental mTBI

Summary

Introduction

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. 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. Blood-based biomarkers hold great promise in the mTBI field, as there are several candidate protein biomarkers that may be indicative of neuronal and glial cell loss, metabolic abnormalities, vascular changes, neuroinflammation, axonal injury, and other pathophysiological mechanisms associated with mTBI11,19–28

Methods

Results

Discussion

Conclusion