Grant: Project Grant

In the healthy brain, neuronal functioning depends on continual tuning of blood flow in proportion to the level of local neuronal activity. A blockage of a major artery during stroke results in a sharp decline in blood flow, killing the neurons and inducing sudden paralysis, impaired speech, and/or loss of vision. Despite the availability of treatments for clot dissolution in the acute and rehabilitation regimens in the chronic stage, most patients suffer significant long-term disabilities and up to a third are institutionalized. Development of more effective therapies is hindered by the uncertainty surrounding the cellular changes required for complete recovery. Recent evidence suggests that the activity of the neurons in the peri-infarct zone, the damaged but potentially salvageable brain region surrounding the site of stroke, greatly influences recovery. Using advanced imaging techniques in rats, we will monitor the function of peri-infarct neurons in the hours following stroke induction. We will inject the brains of these rats with viruses that carry specific membrane channels to allow us to modulate the activity of peri-infarct neurons non-invasively, by illuminating them with light of specific wavelength. These finely controlled experiments will allow us to determine activity levels of these neurons that minimize short- and long-term functional deficits. We will then attempt to achieve comparable activity profiles by tuning the dose of locally delivered novel anti-convulsant medication. These experiments will establish the ways by which brain functioning can be affected early post stroke so as to improve neuronal function. The insights gained will guide the development of next generation, non-invasive treatments that can be readily combined with current therapies to enhance recovery from ischemic stroke.