Submission ID 94301
| Poster Code | HR-P-78 |
|---|---|
| Title of Abstract | Microglial Extracellular Vesicles: Indicators and propagators of post-stroke neuroinflammation |
| Abstract Submission | Microglia are the brain's resident immune cells and play a critical role in the response to neurological injury including stroke. Microglia are highly dynamic, adopting a variety of phenotypes that mediate post-stroke tissue repair and chronic inflammatory signaling. Importantly, a prolonged pro-inflammatory phenotype post-stroke is associated with secondary neurodegeneration and cognitive impairment. Currently, our ability to assess and potentially modify microglia activity post-injury is limited by our inability to clinically measure microglia phenotype. To address this limitation, we used in vitro models to characterize extracellular vesicles released from microglia (MEVs) and validated blood-based measurement of circulating MEVs in a preclinical model of ischemic stroke. MEVs were collected from microglia supernatant in vitro after exposure to lipopolysaccharide (LPS) after which surface protein and cargo were evaluated using qPCR, western blot and transmission electron microscopy. MEVs from LPS-exposed cells were applied to naïve microglia and pro-inflammatory gene expression was measured. Stroke was modeled in 3-month Fischer 344 rats using a focal injection of Endothelin-1 with plasma collected at baseline and 28-days post-injection after which circulating MEV proteins and cargo were measured using nanoflow cytometry. MEVs released from microglia following LPS exposure in vitro have altered surface proteins and carry pro-inflammatory molecules that reflect their phenotype. MEVs released from LPS-exposed cells have signaling capacity and propagate pro-inflammatory signaling to naïve cells in a dose-dependent manner. Circulating MEVs can be rapidly measured in plasma using nanoflow cytometry with antibodies against surface proteins and cargo and remain elevated 28-days post-stroke. The use of circulating MEVs as indicators of microglia activity allows for non-invasive, rapid measurement of microglia phenotype with potential application to many neurological diseases. Future work is required to better understand the relationship between MEVs, pro-inflammatory signaling and neurological outcomes. |
| Please indicate who nominated you | Wenxuan Wang |
| What Canadian Institutes of Health Research (CIHR) institute is your research most closely aligned? | Neurosciences, Mental Health and Addiction |
| What Canadian Institutes of Health Research (CIHR) pillar of health research does your research fall under? | Biomedical |
| PDF of abstract | ICAM Abstract 2023.pdf 2023-03-10 at 06:53:12 |
| Presenter and Author(s) | Austyn Roseborough Sarah Myers Yunxu Zhu Reza Khazaee Lin Zhao Stephen Pasternak Shawn Whitehead |
