Mechanisms and Biomarker Potential of Extracellular Vesicles in Stroke

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.

New Biomarkers for Cardiovascular Disease

“…Because brain tissue is usually unavailable for clinical study in cases of brain injury, biomarkers that can be transported across the blood-brain barrier to the circulatory system offer the unique potential for understanding the pathophysiologic state of the brain tissue after injury to the central nervous system. 34 In a case-control study, exosomal miRNA-223 levels were higher in patients with acute ischemic stroke than in patients without stroke, highlighting the potential of exosomal content as a diagnostic tool for non-CVD diseases with ischemic origin. 35 …”

Cell Type-Specific Extracellular Vesicles and Their Impact on Health and Disease

“…Oligodendrocyte-derived EVs (OD-EVs) have proved to be useful markers of cerebrovascular accidents (strokes). Oligodendrocytes provide an established role in remyelination in post-ischemic injury and influence neuronal survival [ 137 , 138 ]. Fröhlich et al examined the effects of OD-EVs in an oligodendrocyte/neuron co-culture stressed with ischemic injury and saw that cells treated with OD-EVs had significantly higher metabolic activity compared with control cells [ 139 ].…”

“…OD-EVs appeared to contain cargo, including enzymes, such as catalase and superoxide dismutase 1, that provided antioxidant benefits [ 139 ]. Broadly, knowledge of EVs derived from OD-EVs and EVs in the context of stroke remains limited, with more extensive research efforts needed [ 137 ].…”

Zerebrale Mikroangiopathie: Fortschritte im Verständnis der Pathophysiologie

“…Spannende Kandidaten für blutbasierte Biomarker einer hirnspezifischen mikrovaskulären Schädigung sind extrazelluläre Vesikel (EVs). Diese von Zellen abgeleiteten, membranumhüllten Partikel werden von allen Zelltypen im zentralen Nervensystem abgesondert, passieren dann die BHS und enthalten zell-spezifische Marker [41]. Bei kognitiv normalen älteren Menschen mit und ohne Nachweis von WMH in der Bildgebung des Gehirns, konnte eine Assoziation z.…”