Long-term consequences of repetitive concussions: The molecular signature of the point of no return
About the Project
Mild Traumatic Brain Injury (mTBI), also known as Concussion, is a transient disturbance of normal neurological function that results from a rapid rotational acceleration of the brain and showing no gross structural injury using conventional neuroimaging. The cognitive effects of concussion (such as memory problems, communication, personality changes, as well as depression) appear after injury and in most cases improve spontaneously over time. However, in some cases, these changes can persist, especially if multiple concussions are sustained within a vulnerable time period.
Several pre-clinical studies, including ours, using an adult rodent model of repeated weight drop injuries, have shown a window of metabolic derangement post-injury, during which there is an increased vulnerability to further injury. However, it is not known whether repeated concussions are sufficient to increase the brain’s vulnerability to long term neurodegenerative processes.
Despite the growing literature linking mTBI or repeated mTBI (rTBI) to an increased risk of dementia, and particularly frequent in contact and collision sport, data are still unclear and the long-term consequences of sport-related concussion (SRC) are still debated in the scientific community, therefore the need for studies to address the signature of the point of no return that will irreversibly lead to a neurodegenerative condition.
We hypothesise that response of each individual to injury may operate according to a "molecular threshold", beyond which is leading to relentless tissue destruction and functional loss.
With project, using the rodent weight drop model of rTBI and through a series of interlinked experiments we aim to:
- Establish the molecular threshold which irreversibly compromises the brain and determines the point of no return to neurodegeneration
- Explore how epigenetic factors, such as microRNAs, can be involved in this "fatal switch" modulating inflammation and oxidative stress, participating in lipid metabolism, protein cleavage and in neurofilaments homeostasis, whilst altering the balance between apoptotic and growth signals.
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