We Study...
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The Laboratory for Brain Injury and Dementia at Georgetown University uses in vivo brain trauma models to understand how traumatic brain injury (TBI) impacts normal brain function, and why it can result in the activation of pathways involved in chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson’s disease, and Chronic Traumatic Encephalopathy (CTE).
Our overarching goal is to understand how and why severe TBI or repeat mild TBI (mTBI) results in the development of cognitive impairment, behavioral abnormalities, and dementia.
We use advanced techniques including RNA sequencing to unlock how TBI alters our transcriptome, proteomics to discover new protein targets to treat TBI, EEG to visualize how TBI alters brain waves and sleep patterns, and electrophysiology to understand how TBI changes our synapses and communication between neurons. We collaborate with fantastic scientists including Stefano Vicini and Jian-young Wu at Georgetown University, Mark Cookson at NIH, and Tomas Ryan at Trinity College Dublin to discover the mechanisms of TBI and unlock new treatments to prevent brain damage and recover cognitive function.
Head Impact & Concussion
A concussion is a temporary loss of brain function that is spontaneously recoverable. How then can repeat concussions, or even non-concussive head impacts, result in chronic cognitive dysfunction?
A major function of our lab is to better understand how the brain responds to repeated head impact. We design and characterize in vivo models of head impact to better model "real world" conditions, especially the high frequency of head impacts that occur in contact sports.
We use a wide array of techniques to determine how head impacts are altering brain function, including RNA sequencing, patch clamp electrophysiology, EEG, behavior, pharmacology, and molecular biology. We have found that a high frequency of head impacts causes a long-term adaptation in the synapses of the brain that we believe is a protective response, but comes at cost that includes impaired brain function.
Severe TBI, Amyloid & Tau
Why does the TBI brain accumulate neurodegenerative disease proteins including amyloid-beta and hyperphosphorylated tau? We study the pathology of experimental TBI in order to understand the mechanisms that cause the overproduction of these abnormal proteins, and the poor clearance of them from the brain.
We have found that axonal injury is the hotspot of abnormal amyloid and tau production after experimental TBI, and we use genetically modified mice to understand the consequences of this accumulation. APOE4 is best known as a genetic risk factor for Alzheimer's disease, and we see a strong interaction between APOE4 and TBI recovery. APOE4 mice have impaired clearance of amyloid from the TBI brain, slower repair of the injured blood brain barrier, larger loss of brain tissue, and worse behavioral outcomes than APOE3 mice.
Sex Differences in TBI
Most preclincal research occurs in male rodents. New pathways are discovered, and drugs are designed based on this research. But sex matters... and it really matters in TBI research. While the incidence of TBI is higher in males, symptoms can present differently in females and can manifest longer.
We are committed to studying sex as a biological variable in our TBI research. We have found that female mice have a very different neuroinflammatory response in the hours, days, and weeks following a severe TBI, and that the trajectory of brain injury is very different to male mice. Neuroinflammation is one of the top potential therapies to treat TBI, and this strong difference in the inflammatory response will have to be taken into consideration as new therapies are developed.