Project 462340

Neurological disorders are a major contributor to disability worldwide. Their enormous socioeconomic impact continues to grow as the population ages. To date, neurological disorders have no cure, only care. A promising approach to promote neural repair is to harness the potential of resident neural stem cells and their progeny (neural precursor cells) in the brain. Indeed, resident brain precursor cells can be activated to expand in number, migrate and generate new neural cells that are lost to injury or disease, and promote brain repair and functional recovery in some models of injury. We have recently demonstrated that electrical stimulation can activate brain precursors, supporting a role for electrical stimulation in regenerative medicine. Importantly, electrical stimulation is an approved and effective treatment to treat humans with movement disorders such as Parkinson's disease. We propose to repurpose deep brain stimulation therapy to promote tissue regeneration. We will optimize and advance the field of "electroceuticals" by designing novel stimulating electrodes based on optimized parameters for precursor cell activation. Specifically, we will take advantage of a novel slice culture system we have created to optimize the stimulation parameters for precursor cell activation and then design and manufacture multimodal electrodes that not only stimulate the precursor cells but also promote brain plasticity by delivering regenerative factors in a local and controlled fashion. We will examine the biocompatibility and feasibility of our optimized electrodes in control (uninjured) mouse brains and then test their efficacy in a preclinical mouse model of stroke. We will examine cell behaviour as well as clinically relevant, behavioural outcomes. The clinical potential and broad applicability of these electrical stimulation tools to treat neurological disorders holds great promise for treating currently untreatable brain disorders.