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M1 Microglia-Derived Exosomes Promote A1 Astrocyte Activation and Aggravate Ischemic Injury via

Zhongyuan Li1, Pengfei Xu2, Yang Deng3

  • 1Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210000, People's Republic of China.

Journal of Inflammation Research
|November 26, 2024
PubMed
Abstract

Insights

Circular RNA circSTRN3 in exosomes from M1 microglia promotes astrocyte activation and worsens ischemic stroke outcomes. This molecular pathway, involving miR-331-5p and MAVS, offers potential therapeutic targets for stroke.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Ischemic stroke (IS) triggers pro-inflammatory polarization of microglia (M1) and astrocytes (A1).
  • Exosomes mediate intercellular communication between M1 microglia and A1 astrocytes post-IS.

Purpose of the Study:

  • To investigate the role of M1 microglial exosomes in astrocyte activation after ischemic stroke.
  • To identify specific exosomal molecules involved in the M1 microglia-A1 astrocyte crosstalk.
  • To elucidate the underlying molecular mechanisms and therapeutic potential in ischemic brain injury.

Main Methods:

  • Established M1 microglial oxygen-glucose deprivation/reperfusion (OGD/R) model to isolate M1-derived exosomes (M1-exos).
  • Identified enriched circSTRN3 in M1-exos using RNA sequencing and validated its role in astrocyte activation.
  • Utilized bioinformatics, immunofluorescence, Western blotting, and PCR in vitro and in vivo (MCAO/R mouse model) and in IS patient samples.

Main Results:

  • M1-exos significantly promoted A1 astrocyte activation.
  • CircSTRN3, abundant in M1-exos, acts as a sponge for miR-331-5p, impacting the MAVS/NF-κB pathway and driving A1 astrocyte activation.
  • Overexpression of circSTRN3 exacerbated infarct size and neurological deficits in MCAO/R mice, effects reversed by miR-331-5p mimics. CircSTRN3 levels correlated positively with stroke severity in patients, while miR-331-5p levels correlated negatively.

Conclusions:

  • CircSTRN3 derived from M1 microglial exosomes promotes A1 astrocyte activation.
  • This exacerbates ischemic brain injury via the miR-331-5p/MAVS/NF-κB axis.
  • CircSTRN3 and miR-331-5p in peripheral blood exosomes are potential biomarkers for stroke severity.
Keywords:
astrocytecircSTRN3exosomeischemic strokemiR-331-5pmicroglia

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