Unpacking the Role of Extracellular Vesicles in Ischemic and Hemorrhagic Stroke: Pathophysiology and Therapeutic Implications

Hirsch, Yonatan; Geraghty, Joseph R; Reiter, Cory R.; Katz, Eitan; Little, Conner F.; Tobin, Matthew K.; Testai, Fernando D.

doi:10.1007/s12975-022-01027-2

Cited by 7 publications

(2 citation statements)

References 128 publications

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“…Recent studies have shown that EVs play an important role in the pathophysiological process of IS [ 87 , 88 ]. Researchers have found that many different cell-derived EVs have neuroprotective and nerve repair functions.…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles

Gao,

Liu,

Yue

et al. 2024

Biomolecules

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Ischemic stroke is a fatal and disabling disease worldwide and imposes a significant burden on society. At present, biological markers that can be conveniently measured in body fluids are lacking for the diagnosis of ischemic stroke, and there are no effective treatment methods to improve neurological function after ischemic stroke. Therefore, new ways of diagnosing and treating ischemic stroke are urgently needed. The neurovascular unit, composed of neurons, astrocytes, microglia, and other components, plays a crucial role in the onset and progression of ischemic stroke. Extracellular vesicles are nanoscale lipid bilayer vesicles secreted by various cells. The key role of extracellular vesicles, which can be released by cells in the neurovascular unit and serve as significant facilitators of cellular communication, in ischemic stroke has been extensively documented in recent literature. Here, we highlight the role of neurovascular unit-derived extracellular vesicles in the diagnosis and treatment of ischemic stroke, the current status of extracellular vesicle engineering for ischemic stroke treatment, and the problems encountered in the clinical translation of extracellular vesicle therapies. Extracellular vesicles derived from the neurovascular unit could provide an important contribution to diagnostic and therapeutic tools in the future, and more studies in this area should be carried out.

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Section: Extracellular Vesiclesmentioning

confidence: 99%

Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles

Gao,

Liu,

Yue

et al. 2024

Biomolecules

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show abstract

“…Intracerebral hemorrhage (ICH) is a subtype of stroke, which accounts for 10%–15% of all strokes characterized by high mortality and morbidity. 1 , 2 A series of pathophysiological processes, such as brain edema, blood–brain barrier disruption, neuroinflammation, mitochondrial dysfunction, neuronal apoptosis, etc., are triggered by the initial mass mechanical effect of intracerebral hematoma and intrahematoma hemolytic products in ICH brain. 3 , 4 Recently, myriad studies started to focus on the role of various stress events in adaptive response and adverse reactions in neurological diseases.…”

Section: Introductionmentioning

confidence: 99%

The phosphokinase activity of IRE1ɑ prevents the oxidative stress injury through miR‐25/Nox4 pathway after ICH

Liao,

Huang,

Wang

et al. 2023

CNS Neurosci Ther

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BackgroundEndoplasmic reticulum (ER) stress and oxidative stress are the major pathologies encountered after intracerebral hemorrhage (ICH). Inositol‐requiring enzyme‐1 alpha (IRE1α) is the most evolutionarily conserved ER stress sensor, which plays a role in monitoring and responding to the accumulation of unfolded/misfolded proteins in the ER lumen. Recent studies have shown that ER stress is profoundly related to oxidative stress in physiological or pathological conditions. The purpose of this study was to investigate the role of IRE1α in oxidative stress and the potential mechanism.MethodsA mouse model of ICH was established by autologous blood injection. The IRE1α phosphokinase inhibitor KIRA6 was administrated intranasally at 1 h after ICH, antagomiR‐25 and agomiR‐25 were injected intraventricularly at 24 h before ICH. Western blot analysis, RT‐qPCR, immunofluorescence staining, hematoma volume, neurobehavioral tests, dihydroethidium (DHE) staining, H2O2 content, brain water content, body weight, Hematoxylin and Eosin (HE) staining, Nissl staining, Morris Water Maze (MWM) and Elevated Plus Maze (EPM) were performed.ResultsEndogenous phosphorylated IRE1α (p‐IRE1α), miR‐25‐3p, and Nox4 were increased in the ICH model. Administration of KIRA6 downregulated miR‐25‐3p expression, upregulated Nox4 expression, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, reduced body weight, aggravated spatial learning and memory deficits, and increased anxiety levels. Then antagomiR‐25 further upregulated the expression of Nox4, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, whereas agomiR‐25 reversed the effects promoted by KIRA6.ConclusionThe IRE1α phosphokinase activity is involved in the oxidative stress response through miR‐25/Nox4 pathway in the mouse ICH brain.

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Macrophage/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol Against Experimental Intracerebral Hemorrhage in Mice

Sun

Yang

et al. 2023

Cell Mol Neurobiol

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Unpacking the Role of Extracellular Vesicles in Ischemic and Hemorrhagic Stroke: Pathophysiology and Therapeutic Implications

Cited by 7 publications

References 128 publications

Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles

Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles

The phosphokinase activity of IRE1ɑ prevents the oxidative stress injury through miR‐25/Nox4 pathway after ICH

Macrophage/Microglia Sirt3 Contributes to the Anti-inflammatory Effects of Resveratrol Against Experimental Intracerebral Hemorrhage in Mice

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