Mechanisms and Biomarker Potential of Extracellular Vesicles in Stroke

SIMPLE SUMMARY: A stroke occurs when there is a lack of blood flow to the brain. Stroke injures the brain and can have devastating outcomes depending on the size and location of the brain tissue affected. Currently, there are only a limited number of treatment options for stroke. Extracellular vesicles are small vesicles secreted by cells. Importantly, extracellular vesicles have specific markers indicating the cell they were released from and can pass from the brain into the blood. For these reasons, assessing extracellular vesicles in the blood may create a window into changes occurring in the brain. Assessing changes in extracellular vesicles in the blood during stroke may produce new insight into the cellular changes in the brain causing injury during stroke. This in turn may generate potential targets for the development of future treatments. We summarize what is known about changes in brain-cell-specific extracellular vesicles during stroke and stress the importance of continuing to study these changes. ABSTRACT: Stoke is a prevalent and devastating neurologic condition with limited options for therapeutic management. Since brain tissue is rarely accessible clinically, peripheral biomarkers for the central nervous system’s (CNS’s) cellular response to stroke may prove critical for increasing our understanding of stroke pathology and elucidating novel therapeutic targets. Extracellular vesicles (EVs) are cell-derived, membrane-enclosed vesicles secreted by all cell types within the CNS that can freely pass the blood-brain barrier (BBB) and contain unique markers and content linked to their cell of origin. These unique qualities make brain-derived EVs novel candidates for non-invasive blood-based biomarkers of both cell specificity and cell physiological state during the progression of stroke and recovery. While studies are continuously emerging that are assessing the therapeutic potential of EVs and profiling EV cargo, a vast minority of these studies link EV content to specific cell types. A better understanding of cell-specific EV release during the acute, subacute, and chronic stages of stroke is needed to further elucidate the cellular processes responsible for stroke pathophysiology. Herein, we outline what is known about EV release from distinct cell types of the CNS during stroke and the potential of these EVs as peripheral biomarkers for cellular function in the CNS during stroke.