A Model for Mild Traumatic Brain Injury that Induces Limited Transient Memory Impairment and Increased Levels of Axon Related Serum Biomarkers

Elham Rostami,Bo-Michael Bellander,John Walker,Mårten Risling,Jia Lu,Stefan Plantman,Kian Chye Ng,Denes V Agoston,Johan Davidsson,Andrea Gyorgy,Daniel Wingo

doi:10.3389/fneur.2012.00115

Abstract

Mild traumatic brain injury (mTBI) is one of the most common neuronal insults and can lead to long-term disabilities. mTBI occurs when the head is exposed to a rapid acceleration-deceleration movement triggering axonal injuries. Our limited understanding of the underlying pathological changes makes it difficult to predict the outcome of mTBI. In this study we used a scalable rat model for rotational acceleration TBI, previously characterized for the threshold of axonal pathology. We have analyzed whether a TBI just above the defined threshold would induce any detectable behavioral changes and/or changes in serum biomarkers. The effect of injury on sensory motor functions, memory and anxiety were assessed by beam walking, radial arms maze and elevated plus maze at 3–7 days following TBI. The only behavioral deficits found were transient impairments in working and reference memory. Blood serum was analyzed at 1, 3, and 14 days after injury for changes in selected protein biomarkers. Serum levels of neurofilament heavy chain and Tau, as well as S100B and myelin basic protein showed significant increases in the injured animals at all time points. No signs of macroscopic injuries such as intracerebral hematomas or contusions were found. Amyloid precursor protein immunostaining indicated axonal injuries at all time points analyzed. In summary, this model mimics some of the key symptoms of mTBI, such as transient memory impairment, which is paralleled by an increase in serum biomarkers. Our findings suggest that serum biomarkers may be used to detect mTBI. The model provides a suitable foundation for further investigation of the underlying pathology of mTBI.

Highlights

Mild or minor traumatic brain injury is one of the most common neurological disorders and it is estimated to comprise 70–90% of all traumatic brain injuries (Bazarian et al, 1999)
The minor traumatic brain injury (mTBI) patients have a brief period of unconsciousness, but the usual findings at admission to a hospital is Glasgow Coma Scale values of 13–15 and Computer tomography (CT) indicates no detectable injuries (Bazarian et al, 2006)
It is possible that the injuries resulting from some of the potential mTBI subclasses currently are not recognized in clinical practice

Summary

Introduction

Mild or minor traumatic brain injury (mTBI) is one of the most common neurological disorders and it is estimated to comprise 70–90% of all traumatic brain injuries (Bazarian et al, 1999). There are two existing studies where the brain tissue of patients who suffered from mTBI but who subsequently died from other causes has been investigated histologically (Blumbergs et al, 1994, 1995). In both studies axonal damage was demonstrated by amyloid precursor protein (APP) staining, indicating the importance of this pathology in mTBI. Advanced neuroimaging techniques such as diffusion tensor imaging (DTI) have been used to investigate structural changes in patients with mTBI and have showed the presence of axonal injuries (Niogi et al, 2008a,b; Wilde et al, 2008; Chu et al, 2010; Mayer et al, 2010)

Methods

Results

Conclusion