Astrocyte-Derived Extracellular Vesicles for Ischemic Stroke: Therapeutic Potential and Prospective

doi:10.14336/ad.2023.0823-1

Cited by 3 publications

(3 citation statements)

References 247 publications

(275 reference statements)

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“…Glial activation is a double-edged sword, whereby its acute expression may be beneficial [47], but when it occurs chronically, then such gliosis may exacerbate stroke outcomes [48]. Moreover, extracellular vesicles have been implicated in the neuroprotective function of glial cells [49]. In a similar fashion, both neurogenesis and angiogenesis are established neuroprotective and regenerative mechanisms for stroke, especially in the repair of the NVU [50][51][52], with extracellular vesicles becoming widely recognized as contributing to these therapeutic responses [53][54][55].…”

Section: Discussionmentioning

confidence: 99%

Endogenous Extracellular Vesicles Participate in Brain Remodeling after Ischemic Stroke

Alvarez,

Salazar,

Rodriguez

et al. 2023

IJMS

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Brain remodeling after an ischemic stroke represents a promising avenue for exploring the cellular mechanisms of endogenous brain repair. A deeper understanding of these mechanisms is crucial for optimizing the safety and efficacy of neuroprotective treatments for stroke patients. Here, we interrogated the role of extracellular vesicles, particularly exosomes, as potential mediators of endogenous repair within the neurovascular unit (NVU). We hypothesized that these extracellular vesicles may play a role in achieving transient stroke neuroprotection. Using the established ischemic stroke model of middle cerebral artery occlusion in adult rats, we detected a surged in the extracellular vesicle marker CD63 in the peri-infarct area that either juxtaposed or co-localized with GFAP-positive glial cells, MAP2-labeled young neurons, and VEGF-marked angiogenic cells. This novel observation that CD63 exosomes spatially and temporally approximated glial activation, neurogenesis, and angiogenesis suggests that extracellular vesicles, especially exosomes, contribute to the endogenous repair of the NVU, warranting exploration of extracellular vesicle-based stroke therapeutics.

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Section: Discussionmentioning

confidence: 99%

Endogenous Extracellular Vesicles Participate in Brain Remodeling after Ischemic Stroke

Alvarez,

Salazar,

Rodriguez

et al. 2023

IJMS

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“…(33)(34)(35). Exosome cytoplasm involves microRNA (miRNA), long noncoding RNA (lncRNA), messenger RNA (mRNA), proteins, lipids, and lots of other active ingredients (36)(37)(38). Exosomes may deliver the active ingredients, which they convey to the target cells through mutual fusion with the cell membranes of the recipient cells, cytosis, and other modes of action to impact the function of recipient cells (39)(40)(41).…”

Section: Introductionmentioning

confidence: 99%

Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

Qiu,

Lu,

et al. 2024

Front. Immunol.

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Gastric cancer (GC) is a malignant neoplasm originating from the epithelial cells of the gastric mucosa. The pathogenesis of GC is intricately linked to the tumor microenvironment within which the cancer cells reside. Tumor-associated macrophages (TAMs) primarily differentiate from peripheral blood monocytes and can be broadly categorized into M1 and M2 subtypes. M2-type TAMs have been shown to promote tumor growth, tissue remodeling, and angiogenesis. Furthermore, they can actively suppress acquired immunity, leading to a poorer prognosis and reduced tolerance to chemotherapy. Exosomes, which contain a myriad of biologically active molecules including lipids, proteins, mRNA, and noncoding RNAs, have emerged as key mediators of communication between tumor cells and TAMs. The exchange of these molecules via exosomes can markedly influence the tumor microenvironment and consequently impact tumor progression. Recent studies have elucidated a correlation between TAMs and various clinicopathological parameters of GC, such as tumor size, differentiation, infiltration depth, lymph node metastasis, and TNM staging, highlighting the pivotal role of TAMs in GC development and metastasis. In this review, we aim to comprehensively examine the bidirectional communication between GC cells and TAMs, the implications of alterations in the tumor microenvironment on immune escape, invasion, and metastasis in GC, targeted therapeutic approaches for GC, and the efficacy of potential GC drug resistance strategies.

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“…Furthermore, literature on post-stroke EV cargo is predominantly focused on microRNAs, and investigations of the protein content are relatively rare [ 41 ]. Recent evidence suggested that astrocyte-derived EVs (ADEVs) mediate numerous biological processes in stroke, including neuroprotection and neurorepair [ 44 ]. In this pilot study, we aimed to release an ADEV profile of IS patients, focusing on the GFAP as the cargo protein of these EVs in dynamics: 24 h (D1), 7 days (D7), and one month (M1) following the onset of IS.…”

Section: Introductionmentioning

confidence: 99%

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

Forró,

Manu,

Băjenaru

et al. 2024

IJMS

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The utility of serum glial fibrillary acidic protein (GFAP) in acute ischemic stroke (AIS) has been extensively studied in recent years. Here, we aimed to assess its potential role as a cargo protein of extracellular vesicles (EVs) secreted by astrocytes (ADEVs) in response to brain ischemia. Plasma samples from eighteen AIS patients at 24 hours (D1), 7 days (D7), and one month (M1) post-symptoms onset, and nine age, sex, and cardiovascular risk factor-matched healthy controls were obtained to isolate EVs using the Exoquick ULTRA EV kit. Subsets of presumed ADEVs were identified further by the expression of the glutamate aspartate transporter (GLAST) as a specific marker of astrocytes with the Basic Exo-Flow Capture kit. Western blotting has tested the presence of GFAP in ADEV cargo. Post-stroke ADEV GFAP levels were elevated at D1 and D7 but not M1 compared to controls (p = 0.007, p = 0.019, and p = 0.344, respectively). Significant differences were highlighted in ADEV GFAP content at the three time points studied (n = 12, p = 0.027) and between D1 and M1 (z = 2.65, p = 0.023). A positive correlation was observed between the modified Rankin Scale (mRS) at D7 and ADEV GFAP at D1 (r = 0.58, p = 0.010) and D7 (r = 0.57, p = 0.013), respectively. ADEV GFAP may dynamically reflect changes during the first month post-ischemia. Profiling ADEVs from peripheral blood could provide a new way to assess the central nervous system pathology.

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Astrocyte-Derived Extracellular Vesicles for Ischemic Stroke: Therapeutic Potential and Prospective

Cited by 3 publications

References 247 publications

Endogenous Extracellular Vesicles Participate in Brain Remodeling after Ischemic Stroke

Endogenous Extracellular Vesicles Participate in Brain Remodeling after Ischemic Stroke

Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

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

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