Extracellular Vesicle ASC: A Novel Mediator for Lung–Brain Axis in Preterm Brain Injury

Starke, Natalie; Challa, Naga Venkata Divya; Yuan, Huijun; Chen, Shaoyi; Duncan, Matthew R.; Cabrera Ranaldi, Erika D.L.R.M.; de Rivero Vaccari, Juan Pablo; Schott, Alini; Aguilar, Ana Cecilia; Lee, Yee-Shuan; Khan, Aisha; Duara, Jo; Tan, April; Benny, Merline; Schmidt, Augusto F.; Young, Karen; Bancalari, Eduardo; Claure, Nelson; Wu, Shu

doi:10.1165/rcmb.2023-0402oc

Am J Respir Cell Mol Biol

2024

DOI: 10.1165/rcmb.2023-0402oc

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Extracellular Vesicle ASC: A Novel Mediator for Lung–Brain Axis in Preterm Brain Injury

Natalie Starke,

Naga Venkata Divya Challa,

Huijun Yuan

et al.

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Cited by 2 publications

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Brain–Periphery Axes: The Potential Role of Extracellular Vesicles-Delivered miRNAs

D’Amico,

Carista,

Manna

et al. 2024

Biology

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Bidirectional communication between the central nervous system (CNS) and peripheral organs and tissue has been widely documented in physiological and pathological conditions. This communication relies on the bilateral transmission of signaling molecules and substances that circulate throughout the body and reach their target site(s) via the blood and other biological fluids (e.g., the cerebrospinal fluid, the lymph). One of the mechanisms by which these molecular messengers are exchanged is through the secretion of extracellular vesicles (EVs). EVs are known to mediate cell-to-cell communication by delivering biological molecules, including nucleic acids, proteins, lipids, and various other bioactive regulators. Moreover, EVs can cross the blood–brain barrier (BBB), enabling direct communication between the periphery and the brain. In particular, the delivery of microRNAs (miRNAs) can modulate the expression profiles of recipient cells, thereby influencing their functions. This review synthesizes current findings about the brain–periphery cross-talk mediated by EVs-delivered miRNAs. Although this mechanism has been definitively shown in a few cases, much evidence indirectly indicates that it could mediate brain–peripherical organs/tissue communication, especially in pathological conditions. Therefore, understanding this process could provide valuable insights for the treatment and management of neurological and systemic diseases.

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Brain–Periphery Axes: The Potential Role of Extracellular Vesicles-Delivered miRNAs

D’Amico,

Carista,

Manna

et al. 2024

Biology

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Unveiling the Emerging Role of Extracellular Vesicle–Inflammasomes in Hyperoxia-Induced Neonatal Lung and Brain Injury

Young,

Benny,

Schmidt

et al. 2024

Cells

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Extremely premature infants are at significant risk for developing bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). Although BPD is a predictor of poor neurodevelopmental outcomes, it is currently unknown how BPD contributes to brain injury and long-term NDI in pre-term infants. Extracellular vesicles (EVs) are small, membrane-bound structures released from cells into the surrounding environment. EVs are involved in inter-organ communication in diverse pathological processes. Inflammasomes are large, multiprotein complexes that are part of the innate immune system and are responsible for triggering inflammatory responses and cell death. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is pivotal in inflammasome assembly and activating inflammatory caspase-1. Activated caspase-1 cleaves gasdermin D (GSDMD) to release a 30 kD N-terminal domain that can form membrane pores, leading to lytic cell death, also known as pyroptosis. Activated caspase-1 can also cleave pro-IL-1β and pro-IL-18 to their active forms, which can be rapidly released through the GSDMD pores to induce inflammation. Recent evidence has emerged that activation of inflammasomes is associated with neonatal lung and brain injury, and inhibition of inflammasomes reduces hyperoxia-induced neonatal lung and brain injury. Additionally, multiple studies have demonstrated that hyperoxia stimulates the release of lung-derived EVs that contain inflammasome cargos. Adoptive transfer of these EVs into the circulation of normal neonatal mice and rats induces brain inflammatory injury. This review focuses on EV–inflammasomes’ roles in mediating lung-to-brain crosstalk via EV-dependent and EV-independent mechanisms critical in BPD, brain injury, and NDI pathogenesis. EV–inflammasomes will be discussed as potential therapeutic targets for neonatal lung and brain injury.

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Extracellular Vesicle ASC: A Novel Mediator for Lung–Brain Axis in Preterm Brain Injury

Cited by 2 publications

References 70 publications

Brain–Periphery Axes: The Potential Role of Extracellular Vesicles-Delivered miRNAs

Brain–Periphery Axes: The Potential Role of Extracellular Vesicles-Delivered miRNAs

Unveiling the Emerging Role of Extracellular Vesicle–Inflammasomes in Hyperoxia-Induced Neonatal Lung and Brain Injury

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