Date(s) - 10/22/2018
Deep Brain Stimulation (DBS) is a well-established therapy for patients with PD and is an emerging therapy for neuropsychiatric disorders. Despite the rise in DBS usage, relatively little is known about the tissue and cellular responses to DBS. The role of glial cells in the pathogenesis of PD and other conditions of the central nervous system (CNS) is well known. Less clear are the changes in these cells in response to invasive therapeutic interventions for diseases, which is an issue as we enter a new era of novel treatments including DBS, cell transplants, gene therapies and growth factor infusions. To date, all of these treatments have resulted in variable outcomes, but the host glial response induced by such invasively delivered agents has not been addressed in any detail. The UF DBS Brain Bank repository currently has 65 brains, using which we have examined post-mortem effects of DBS leads by objectively quantifying gliosis around the distal DBS lead tip. We hope to provide a better understanding of the extent and nature of cellular response to DBS, which in turn could lead to modifications in the way these therapeutic interventions are delivered.
Research in my lab focuses on comprehending mechanisms of neuronal demise in neurodegenerative diseases in order to improve therapeutic strategies for their treatment. Specifically, there are three main thrust areas to my work: 1) Studying the effect of chronic electrical stimulation [such as Deep Brain Stimulation, DBS] on the neurogenic niches of the brain, and comprehending the cellular-molecular processes affected via this surgical procedure. This work involves the use of both animal models of DBS in neurodegenerative disease [Parkinson’s and Ataxia], as well as post-mortem human tissue taken from patients who suffered from neurodegenerative disorders, including Alzheimer’s disease, Huntington’s disease, Essential Tremor and Parkinson’s disease who have undergone deep brain stimulation (DBS). This work involves tissue analysis using a combination of approaches including imaging and molecular analyses to tease out which cellular subtypes are involved in and responsible for DBS-induced clinical benefits seen in patients. 2) To develop a novel immunomodulatory platform for the treatment of PD and to identify the role of the peripheral immune system in the efficacy of this therapeutic platform [in a preclinical model]. 3) Understanding the brain “metabolome” in disease. Through collaborative work, I have extracted brain tissue from both animals as well as postmortem human brain of Parkinson’s disease, for metabolomics analyses. I am specifically interested in gleaning information from minute fluxes within the brain metabolome of diseased, non-diseased and DBS treated brains.