Abstract
Repeated mild traumatic brain injury (rmTBI), the most common type of traumatic brain injuries, can result in neurological dysfunction and cognitive deficits. However, the molecular mechanisms and the long-term consequence of rmTBI remain elusive. In this study, we developed a modified rmTBI mouse model and found that rmTBI-induced transient neurological deficits and persistent impairments of spatial memory function. Furthermore, rmTBI mice had long-lasting detrimental effect on cognitive function, exhibiting memory deficits even 12 weeks after rmTBI. Microarray analysis of whole genome gene expression showed that rmTBI significantly altered the expression level of 87 genes which are involved in apoptosis, stress response, metabolism, and synaptic plasticity. The results indicate the potential mechanism underlying rmTBI-induced acute neurological deficits and its chronic effect on memory impairments. This study suggests that long-term monitoring and interventions for rmTBI individuals are essential for memory function recovery and reducing the risk of developing neurodegenerative diseases.
Highlights
Traumatic brain injury (TBI), a brain damage caused by an external mechanic force, is a serious issue to public health
Acute neurological impairment is not exaggerated by Repeated mild traumatic brain injury (rmTBI)
The duration of loss of righting reflex (LORR) was not altered by the number of injuries, 100.94 ± 4.51 seconds after 25th mild TBI (mTBI) compared with 98.71.70 ± 4.87 seconds on day 1, p > 0.05 (Fig. 1B)
Summary
Traumatic brain injury (TBI), a brain damage caused by an external mechanic force, is a serious issue to public health It is the leading cause of death and disability for people under 45. It is imperative to determine the long-term impairment-induced by rmTBI, define the underlying molecular mechanisms, and develop effective intervention approaches or treatments. Animal models of mTBI are valuable tools to investigate cellular and molecular mechanisms of mTBI and to monitor long-term effects of mTBI on cognitive functions. Increased animal model-based studies of mTBI have been reported, most of them focused on short-term effect, in the range of hours to 10 days post-mTBI16–18. A few studies showed that long-term changes can last for more than 1 year after mTBI in animals and patients[19,20,21,22]. TBI, including rmTBI, even occurring at young age, significantly increases the risk of neurodegenerative diseases[1,2,3]
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