Repetitive Mild Traumatic Brain Injury Exacerbates Cognitive Deficits in a Mouse Model of Cerebral Amyloid Angiopathy
Abstract
Traumatic brain injury (TBI) affects around 69 million people each year, with mild TBIs (mTBIs) making up the majority of cases. These injuries, often sustained during contact sports, military service, or incidents of domestic violence, typically involve brief or no loss of consciousness and few immediate symptoms. However, repeated occurrences significantly elevate the risk for long-term complications, including dementia. While repetitive in mTBI is strongly linked to chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD), the relationship with cerebral amyloid angiopathy (CAA), characterized by the accumulation of amyloid peptides in the cerebral vasculature, remains understudied. Given that CAA significantly contributes to dementia and stroke risk, it is critical to investigate whether and how repetitive mTBIs exacerbate the development and profession of CAA pathology and associated cognitive-behavioral deficits. In this study, male and female Tg-SwDI mice (CAA model) and wild-type (WT) C57BL/6J controls were exposed to repetitive mTBIs (one hit daily using a modified weight drop method over five consecutive days) starting at approximately two months of age (late adolescence/early adulthood). Cognitive-behavioral outcomes (open field, elevated zero maze, novel object recognition, object placement test, y-maze, and Barnes maze) were assessed 7 days or 3 months post-injury. Repetitive mTBIs resulted in significant impairments in several cognitive tests, with deficits being genotype-, sex-, and time-dependent, with more severe deficits results from mTBI in Tg-SwDI mice, females, and at the later time-point. Our results suggest that even mTBI can result in cognitive deficits and exacerbate symptoms associated with CAA, warranting further investigation of the mechanisms responsible to help identify novel therapeutic targets.
Faculty Sponsors
Dr. Lisa Robinson, Dr. William Kochen, Dr. Benedict Albensi
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-1-2026 12:00 AM
End Date
4-2-2026 12:00 AM
Repetitive Mild Traumatic Brain Injury Exacerbates Cognitive Deficits in a Mouse Model of Cerebral Amyloid Angiopathy
Alvin Sherman Library
Traumatic brain injury (TBI) affects around 69 million people each year, with mild TBIs (mTBIs) making up the majority of cases. These injuries, often sustained during contact sports, military service, or incidents of domestic violence, typically involve brief or no loss of consciousness and few immediate symptoms. However, repeated occurrences significantly elevate the risk for long-term complications, including dementia. While repetitive in mTBI is strongly linked to chronic traumatic encephalopathy (CTE) and Alzheimer's disease (AD), the relationship with cerebral amyloid angiopathy (CAA), characterized by the accumulation of amyloid peptides in the cerebral vasculature, remains understudied. Given that CAA significantly contributes to dementia and stroke risk, it is critical to investigate whether and how repetitive mTBIs exacerbate the development and profession of CAA pathology and associated cognitive-behavioral deficits. In this study, male and female Tg-SwDI mice (CAA model) and wild-type (WT) C57BL/6J controls were exposed to repetitive mTBIs (one hit daily using a modified weight drop method over five consecutive days) starting at approximately two months of age (late adolescence/early adulthood). Cognitive-behavioral outcomes (open field, elevated zero maze, novel object recognition, object placement test, y-maze, and Barnes maze) were assessed 7 days or 3 months post-injury. Repetitive mTBIs resulted in significant impairments in several cognitive tests, with deficits being genotype-, sex-, and time-dependent, with more severe deficits results from mTBI in Tg-SwDI mice, females, and at the later time-point. Our results suggest that even mTBI can result in cognitive deficits and exacerbate symptoms associated with CAA, warranting further investigation of the mechanisms responsible to help identify novel therapeutic targets.
