Abstract
Concussion or mild traumatic brain injury is the most common form of traumatic brain injury with potentially long-term consequences. Current objective diagnosis and treatment options are limited to clinical assessment, cognitive rest, and symptom management, which raises the real danger of concussed patients being released back into activities where subsequent and cumulative injuries may cause disproportionate damages. This study conducted a cross-sectional multi-modal examination investigation of the temporal changes in behavioural and brain changes in a mouse model of concussion using magnetic resonance imaging. Sham and concussed mice were assessed at day 2, day 7, and day 14 post-sham or injury procedures following a single concussion event for motor deficits, psychological symptoms with open field assessment, T2-weighted structural imaging, diffusion tensor imaging (DTI), neurite orientation density dispersion imaging (NODDI), stimulus-evoked and resting-state functional magnetic resonance imaging (fMRI). Overall, a mismatch in the temporal onsets and durations of the behavioural symptoms and structural/functional changes in the brain was seen. Deficits in behaviour persisted until day 7 post-concussion but recovered at day 14 post-concussion. DTI and NODDI changes were most extensive at day 7 and persisted in some regions at day 14 post-concussion. A persistent increase in connectivity was seen at day 2 and day 14 on rsfMRI. Stimulus-invoked fMRI detected increased cortical activation at day 7 and 14 post-concussion. Our results demonstrate the capabilities of advanced MRI in detecting the effects of a single concussive impact in the brain, and highlight a mismatch in the onset and temporal evolution of behaviour, structure, and function after a concussion. These results have significant translational impact in developing methods for the detection of human concussion and the time course of brain recovery.
Highlights
MethodsStudy design This is a cross-sectional study which included a total of 43 3–4 months old (mice age on impact date: 13.2 ± 1.4 weeks) male mice
Concussion, or mild traumatic brain injury, is a physical trauma-induced pathophysiological process affecting the brain, resulting in rapid onset of typically transient neurological dysfunction, with or without loss of consciousness [1]
Imaging findings varied; diffusion tensor imaging (DTI) and neurite orientation density dispersion imaging (NODDI) changes peaked at day 7 and significantly reduced at day 14 post-concussion while the functional connectivity increased at day 2 and 14 post-concussion
Summary
Study design This is a cross-sectional study which included a total of 43 3–4 months old (mice age on impact date: 13.2 ± 1.4 weeks) male mice. Mice were divided into four cohorts: Sham (n = 14, n = 6 day 2, n = 3 day 7, n = 5 day 14), concussion day 2 (CON 2; n = 9), concussion day 7 (CON 7; n = 10), concussion day 14 (CON 14; n = 10). The sham animals underwent the exact same procedure but did not receive an impact. After the concussion or sham procedure, the loss-of-righting-reflex (LRR) time was measured for each of the animals. At day 2, day 7, or day 14, depending on the cohort, the NSS was measured again and all mice underwent Open Field Assessment and MRI scan. Animals were excluded from this study if obvious brain injuries or structural abnormalities were observed on T2-weighted structural MRI images. All experiments were approved by the Institutional Animal Ethics Committee at the University of Queensland (Animal Ethics Committee approval number QBI/260/17)
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