My lab studies rodent models of stroke recovery using optogenetic tools to map the brain, and detailed behavioural measures to assess functional impairments and recovery. Our goal is to develop therapeutic brain stimulation paradigms that may be combined with rehabilitation to enhance recovery after adult and neonatal stroke. Specifically, our ongoing projects are:
Finding the right target: Identifying effective stimulation targets following perinatal stroke.
Approximately 1 in 1500 newborns delivered at term have a stroke, and most of these children are diagnosed with Hemiplegic Cerebral Palsy (HCP) or other sensorimotor impairments. Seminal studies performed in children with perinatal stroke have shown that combining rehabilitation with non-invasive brain stimulation (tDCS) improves function more than either rehabilitation or stimulation applied alone. However, the effects were modest in size and there is a significant need for understanding the mechanisms by which this intervention works. Dr. Silasi has extensive experience applying optogenetic tools in rodent models of stroke to assess the motor system and behavioural recovery. The Silasi lab will now apply these tools in a model of perinatal stroke to systematically evaluate the effectiveness of stimulation targets in both the intact and injured hemispheres. Although therapeutic brain stimulation has been evaluated in models of adult stroke in rodents, this will be the first study focused on identifying optimal treatment targets following developmental stroke.
Assessing the functional impact of microinfarcts.
Stroke is typically viewed as a sudden impairment in blood flow leading to neuronal dysfunction and impairments. Recent data from the world of clinical imaging and pathology have revealed a previously underappreciated phenomenon. Almost invariably, patients that experience a focal ischemic stroke also have a number of smaller microinfarcts that likely occurred before the major stroke. These microinfarcts are less than 1mm in diameter and may be distributed throughout the grey and white matter. Importantly, imaging studies performed on adults over 65 years old revealed that up to 30% of normally-aging individuals have microinfarcts. These findings raise several important questions about the predictive value of microinfarcts for stroke, but also about the impact of microinfarcts on the recovery profile of individuals. Animal models typically induce a single focal insult when testing therapeutics, however based on the clinical findings this model may not be representative. During his post-doctoral training, Dr. Silasi developed a mouse model of diffuse microinfarction that produces detectable damage similar to what is observed clinically. The Silasi Lab will utilize this model to study the impact of diffuse microinfarction on the efficacy of rehabilitation and brain stimulation based interventions after focal stroke.