David L. Brody, MD, PhD
Research in our laboratory and collaborative group is focused on the development of novel diagnostic and therapeutic strategies for traumatic brain injury (TBI). TBI is a major cause of morbidity and mortality worldwide, a major risk factor for the development of Alzheimer's Disease, and the single leading cause of permanent disability in people under age 45 in the United States. There are two major lines of research in the laboratory. The first is focused on uncovering mechanisms underlying amyloid-beta and tau pathologies following traumatic brain injury. Amyloid-beta is believed to play a central role in the development of Alzheimer's Disease, the most common cause of late-life dementia. Tau pathology is a hallmark of Chronic Traumatic Encephalopathy, which affects many former athletes in contact sports who have suffered multiple concussions (e.g. football players, boxers). We have developed experimental models of post-traumatic amyloid-beta and tau pathologies using transgenic mice. The laboratory uses two models of traumatic brain injury: controlled cortical impact and repetitive concussive impact. Using these models, we are working to test hypotheses regarding the mechanisms underlying injury-related accelerations of amyloid-beta and tau pathologies. We are also exploring genetic risk factors for poor outcomes following TBI such as Apolipoprotein E. From there we hope to develop novel therapeutic strategies to alleviate or prevent these pathologies in mice first, then later in humans. The translational focus of the laboratory is exemplified by our use of microdialysis to elucidate amyloid-beta dynamics following TBI in both mice and human patients in a directly comparable fashion. The second major line of research is focused on the detection of traumatic axonal injury using a new MRI technique called Diffusion Tensor Imaging (DTI). Again, this method can be used in both mice and humans in a directly comparable fashion. We have validated this method in a mouse model of TBI using direct, quantitative comparison of DTI signal abnormalities to histological and electron microscopic "gold-standards." DTI appears to be considerably more sensitive to white matter injury than conventional imaging methods. Ongoing work focuses on the use of DTI and another advanced MRI method called functional connectivity MRI in human TBI patients. The goals are to use these methods to improve our ability to detect clinically significant axonal injury after injury, assist with prognosis, and guide stratification of patients for therapeutic trials. The laboratory has provided consultative guidance to the Dept. of Defense and the National Football League on this topic. Collaborations with United States Military researchers at Landstuhl Regional Medical Center in Landstuhl Germany to study the effects of blast-related TBI in active duty US military personnel are underway. The relationship between traumatic brain injury and post-traumatic stress disorder is an area of intense focus at present. Validation of DTI in post-mortem human brains and exploration of genetic risk factors are additional areas of current interest.