Extracellular Vesicles in Acute Stroke Diagnostics

Abstract

There is a large unmet need for fast and reliable diagnostics in several diseases. One such disease is stroke, where the efficacy of modern reperfusion therapies is highly time-dependent. Diagnosis of stroke and treatment initiation should be performed as soon as possible, and preferably before arrival at the stroke center. In recent years, several potential blood biomarkers for stroke have been evaluated, but without success. In this review, we will go into detail on the possibility of utilizing extracellular vesicles (EVs) released into the blood as novel biomarkers for stroke diagnostics. EVs are known to reflect the immediate state of the secreting cells and to be able to cross the blood–brain barrier, thus making them attractive as diagnostic biomarkers of brain diseases. Indeed, several studies have reported EV markers that enable differentiation between stroke patients and controls and, to a lesser extent, the ability to correctly classify the different stroke types. Most of the studies rely on the use of sophisticated and time-consuming methods to quantify specific subpopulations of the nanosized EVs. As these methods cannot be easily implemented in a rapid point of care (POC) test, technical developments followed by prospective clinical studies are needed.

Circulating Extracellular Vesicle Proteins and MicroRNA Profiles in Subcortical and Cortical-Subcortical Ischaemic Stroke

“…Most research studies on stroke have focused on the cortical neuronal ischaemic cascade but have ignored the subcortical damage with the involvement of white matter fibre and oligodendrocytes. Studying the subtypes of stroke that affect different locations, such as subcortical (SC) and cortical-subcortical (CSC) ischaemic stroke, could provide information on the involved damage and repair processes, depending on the affected cell type [12].…”

Brain-Derived Extracellular Vesicles in Health and Disease: A Methodological Perspective

“…In this context, it seems clear that EVs detected in CSF, plasma or blood could be valuable biomarkers of disease prognosis [63,64]. Moreover, treatment with EVs derived from mesenchymal stem cells (MSCs) shows promising results in improving the neurological outcome in animal models of stroke [65], and TBI, through a not-yet well-defined mechanism.…”

“…In other neurological conditions, such as ischemic stroke (IS) and traumatic brain injury (TBI), where initial localized damage (either by the blockage of a main brain artery or by a blow, bump, jolt or a penetrating object to the head) is followed by neuroinflammation, breakage of the blood–brain barrier (BBB), and infiltration of peripheral immune cells, the role of EVs in the disease outcome is much more complex (reviewed in [ 58 , 59 , 60 , 61 , 62 ]). In this context, it seems clear that EVs detected in CSF, plasma or blood could be valuable biomarkers of disease prognosis [ 63 , 64 ]. Moreover, treatment with EVs derived from mesenchymal stem cells (MSCs) shows promising results in improving the neurological outcome in animal models of stroke [ 65 ], and TBI, through a not-yet well-defined mechanism.…”

Living Proof of Activity of Extracellular Vesicles in the Central Nervous System

“…In vivo research has mainly focused on using these released EVs as biomarkers, or in utilizing mesenchymal stromal cell-derived EVs for the treatment of stroke. These developments are reviewed elsewhere [ 66 , 67 ] and beyond the scope of this review.…”