Elevation of astrocyte-derived extracellular vesicles over the first month post-stroke in humans

Abstract

We sought to identify alterations in the quantity of plasma brain-derived extracellular vesicles (EV) over the first month post-stroke to shed light on related injury and repair mechanisms. We assessed plasma levels of presumed neuron-derived EVs (NDEs), astrocyte-derived EVs (ADEs), and oligodendrocyte-derived EVs (ODEs) in 58 patients 5, 15, and 30 days post-ischemic stroke and 46 controls matched for cardiovascular risk factors using sandwich immunoassays. Subsets of brain-derived EVs were identified by co-expression of the general EV marker CD9 and markers for neurons (L1CAM, CD171), astrocytes (EAAT1), and oligodendrocytes (MOG) respectively. Clinical MRIs assessed lesion volume and presence of hemorrhagic transformation. ADE levels were elevated 5, 15, and 30 days post-stroke compared to controls (p = 0.002, p = 0.002, and p = 0.005 respectively) with no significant change for NDE or ODE. ADEs were increased 15 days post-stroke in patients with hemorrhagic transformation (p = 0.04) compared to patients with no hemorrhage. We conclude that ADE levels are preferentially increased over the first month post-stroke in humans, possibly to provide trophic support to injured neurons following ischemia. ADEs hold potential as biomarkers of blood–brain barrier breakdown and hemorrhagic transformation, but this requires further study at earlier time points post-stroke.

GFAP as Astrocyte-Derived Extracellular Vesicle Cargo in Acute Ischemic Stroke Patients—A Pilot Study

“…Astrocytes are critical factors in mediating ischemic damage, with many functions regulated by cellular cross talk through EVs. A recent study revealed preferentially increased ADEV levels over the first month (from 5 to 30 days) post-IS in humans, possibly due to their trophic support on ischemia-damaged neurons; still, the cargo of these EVs has not been assessed [ 45 ]. As a highly specific marker of astrocyte activation, the GFAP is considered a promising prognostic biomarker with clinical utility [ 46 ].…”

“…One of the reasons may be that five out of the nine patients receiving thrombolysis had ischemic lesions on CT scans at D1 after stroke onset. Similarly, a recent study assessing ADEV levels in IS patients—but not their cargo—found no significant differences between participants who did or did not receive IV tPA (alteplase) [ 45 ].…”