Safar Center collaborator Dr. Milos Ikonomovic will soon begin a fascinating new project funded by a grant from the Veterans Administration. The study, “Multifunctional rehabilitative therapy to reduce Alzheimer pathology after TBI,” will examine how environment enrichment therapy (EE), the preclinical analogue to human rehabilitation, affects traumatic brain injury induced accumulation of Alzheimer’s disease-related pathology including accumulation of amyloid-β (Aβ), tau hyper-phosphorylation, synaptic loss, and the degree to which this multifunctional therapeutic approach improves neurobehavioral recovery. These questions will be addressed in a pre-clinical model using controlled cortical impact injury and a unique transgenic mouse expressing human Aβ. The study will also investigate the correlation of epigenetic factors with TBI-induced neuropathology/neurological dysfunction and the recovery promoting effects of EE and EE/simvastatin therapy.
Dr. Ikonomovic, an Associate Professor in the Departments of Neurology and Psychiatry at the University of Pittsburgh, will be collaborating with Safar Center faculty members Drs. Clark, Dixon, Kline, and Kochanek on this project. The study extends the group’s previous published studies in both TBI patients and experimental TBI in animal models which demonstrated that increased brain concentration of Aβ is a key neuropathological link between TBI and Alzheimer’s disease, and is also a therapeutic target. The investigators expect that their newly funded studies will provide insight into the role of novel mechanistic pathways underlying the effects of EE therapy, and that their unique multifunctional therapy approach involving non-invasive intervention and a clinically well-tolerated pharmacotherapy will provide dual benefit by both improving the rehabilitation and reducing the risk of developing Alzheimer pathology after TBI. These data will be critical to guide future clinical trials using EE and simvastatin to enhance rehabilitation after TBI and reduce risk of developing Alzheimer’s disease.