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

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.

Time-Dependent Changes in Serum Level of Protein Biomarkers after Focal Traumatic Brain Injury

“…The results from the present study contrast our previous observations in the rotational type TBI [24]. The two different models result in different types of tissue damage [24][25][26].…”

“…For comparison we have included data from our previous study on rotational TBI. That type of injury results in traumatic axonal injuries in the white matter [24] resembling diffuse axonal injuries (DAI). As seen in Table 1 and Figure 1-3 S100B and MBP.…”

“…The two different models result in different types of tissue damage [24][25][26]. The rotational acceleration TBI induces axonal injury detected by β-APP staining as early as 2h post-injury.…”

“…After that no significant difference were obtained between sham and controls the log10 values obtained for each biomarker in injured animals were normalized (z-transformation) in comparison to values obtained from normal controls. In order to compare the two different TBI models previous data from rotational TBI model [24] was compared to results obtained in current study. For each of the biomarkers, a two-way ANOVA on log10 values was performed with Time (day1, day3 and day14) and group (rot-TBI, Figures 1-3.…”

“…We have previously reported on the serum levels of Tau, NF-H, MBP and S100B in a rotational acceleration TBI (rot-TBI) model that mimics mild TBI [24,25]. Axonal injury detected by β-APP was a hallmark of this injury with no signs of contusion or hemorrhages.…”