Novel strategies to improve stroke outcome
- Years funded:
- 2019 - 2020
Stroke is a leading cause of morbidity and mortality worldwide. Despite its recognised debilitating neurological deficits, the major cause of death after stroke is infection. In fact, bacterial infection is the most frequent medical complication in stroke patients, and it is now increasingly accepted that stroke results in the impairment of host immune defence.
Based on my findings published in Science and Nature Medicine, the overarching aim of my research is to decipher the underlying mechanisms that regulate post-stroke immune impairment, and associated life-threatening sequelae of overwhelming infection. Specifically, I will use well-established mouse models of stroke and innovative imaging methods to determine whether immune impairment after stroke is mediated via downstream effects of selective immune cells and/or through the direct effect of the sympathetic nervous system activation. Furthermore, I will assess whether administration of novel immune cell targeting drugs can modify host immunity in such a way as to restore host antibacterial function and thereby limit bacterial infection after stroke.
In addition, I discovered the majority of bacteria found in tissues of human and mice after stroke are common commensal normally resident within the gut. Thus, I will test whether novel agents that strengthen gut barrier integrity will reduce gut permeability, and inhibit the translocation and dissemination of gut bacteria to sites where they play pathogenic roles. Taken together, these studies will reveal the signalling pathways leading up to the impaired immune defence against bacterial infection after stroke, and have the potential to identify completely novel pharmacological strategies for limiting this important cause of morbidity and mortality in stroke patients. Identifying a new and better targeted approach to reduce bacterial infection in stroke patients will bypass the growing problem of antibiotic resistance, ultimately improving patient outcomes
Dr Connie Wong