The Doyle lab investigates the role of the immune system in causing dementia after stroke. Up to 30% of stroke patients develop dementia in the months and years after their stroke and we are testing the hypothesis that in some patients this is due to a chronic inflammatory response that persists at the site of the stroke lesion. We suspect that in the weeks, months and possibly years after stroke, neurotoxic inflammatory mediators, including T cells, cytokines and antibodies, leak out of the stroke lesion and cause bystander damage to surrounding tissue, which then both impairs recovery, and in some instances leads to cognitive decline. In support of this hypothesis we have data that demonstrates that inflammation persists for months at the site of the lesion after stroke, and that a single stroke can directly lead to the development of immune-mediated delayed cognitive deficits. We are currently in the process of targeting different components of the prolonged inflammatory response to stroke to determine if post stroke dementia can be treated by selectively ablating individual immune mediators such as B lymphocytes, T lymphocytes, and CCR2.
We are also using different mouse strains and human post mortem tissue to investigate how much diversity there is in the inflammatory response to stroke, and map how it is altered by genetics, age and common stroke comorbidities. Related to this, we are interested in developing tools that can be used to track inflammation in the injured CNS by biomedical imaging. In the era of personalized medicine it is vital that we have tools that can be used to identify how the immune system of a patient is responding to their stroke so that we can tailor immune modifying drugs to individual need.
Using the mouse model of post stroke dementia that Dr Doyle developed during his post doctoral training with Dr Marion Buckwalter, we are also mapping the pathological changes that occur in non-infarcted areas of the brain surrounding a stroke lesion in the weeks after stroke, and testing if neurotrophic drugs can mitigate these changes. The rationale for this project is that our end goal is a two-pronged treatment for chronic inflammation after stroke. The first prong is personalized treatment of the inflammatory response, and the second prong is the administration of neurotrophic drugs to augment neuronal survival while treatment of the inflammatory response is underway.