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Updated: Apr 16, 2026

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Astrocyte-mediated ischemic tolerance.

Yuri Hirayama1, Yuri Ikeda-Matsuo2, Shoji Notomi3

  • 1Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine and Department of Liaison Academy, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|March 6, 2015
PubMed
Summary

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Astrocytes, not neurons, are essential for inducing brain ischemic tolerance through preconditioning. This protective effect involves P2X7 receptor upregulation in astrocytes, lasting for weeks.

Area of Science:

  • Neuroscience
  • Cellular Biology
  • Neuroprotection

Background:

  • Preconditioning (PC) induces brain ischemic tolerance, protecting neurons from damage.
  • Previous research primarily focused on neuron-centric mechanisms of ischemic tolerance.

Purpose of the Study:

  • To investigate the role of astrocytes in preconditioning-induced brain ischemic tolerance.
  • To elucidate the molecular mechanisms, particularly the P2X7 receptor, involved in astrocyte-mediated ischemic tolerance.

Main Methods:

  • Utilized a middle cerebral artery occlusion model in mice.
  • Administered fluorocitrate to inhibit astrocytes.
  • Examined P2X7 receptor expression and utilized P2X7 receptor knockout mice.
  • Investigated the role of hypoxia-inducible factor-1α.
Keywords:
HIF-1αP2X7 receptorastrocytesischemic toleranceneuroprotectionpreconditioning

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Main Results:

  • Astrocytic activation, not microglial, correlated with ischemic tolerance induction and lasted over 8 weeks.
  • Inhibiting astrocytes abolished ischemic tolerance.
  • P2X7 receptor upregulation was observed in activated astrocytes.
  • PC-induced ischemic tolerance was abrogated in P2X7 receptor knockout mice.

Conclusions:

  • Astrocytes play a critical and indispensable role in inducing brain ischemic tolerance via preconditioning.
  • Upregulation of the P2X7 receptor in astrocytes is essential for this protective mechanism.
  • Hypoxia-inducible factor-1α is implicated in P2X7 receptor-mediated ischemic tolerance.