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Purinergic signalling in brain ischemia.

Felicita Pedata1, Ilaria Dettori1, Elisabetta Coppi2

  • 1Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy.

Neuropharmacology
|November 20, 2015
PubMed
Summary

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This study explores the roles of adenosine and ATP receptors in brain ischemia. Targeting specific purinergic receptors offers potential therapeutic strategies for neuroprotection and reducing neuroinflammation after ischemic events.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • Ischemia triggers glutamate excitotoxicity and neuroinflammation, leading to secondary brain injury.
  • Extracellular adenosine and ATP levels rise during ischemia, activating P1 and P2 receptors.
  • Purinergic signaling pathways are critical in the evolving cascade of ischemic brain damage.

Purpose of the Study:

  • To review the multifaceted roles of adenosine (P1) and ATP (P2) receptors in ischemic stroke.
  • To evaluate the therapeutic potential of targeting specific purinergic receptor subtypes for neuroprotection and neuroregeneration.
  • To highlight strategies for modulating purine concentrations at injury sites.

Main Methods:

  • Literature review of studies investigating purinergic signaling in cerebral ischemia.
Keywords:
ATPAdenosineCerebral ischemiaOxygen glucose deprivationP1 receptorsP2 receptors

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  • Analysis of receptor subtype functions (A1, A2A, A2B, A3, P2X7, P2Y12) in ischemic conditions.
  • Evaluation of therapeutic interventions targeting purinergic pathways.

    • Main Results:

    • Adenosine via A1 receptors is neuroprotective, but A1 agonists have peripheral side effects.
    • A2A receptor antagonists reduce excitotoxicity; A2A/A2B/A3 agonists mitigate neuroinflammation.
    • P2X7 receptor antagonism may reduce ischemic damage and promote repair; P2Y12 antagonists offer antiplatelet and anti-inflammatory benefits.

    Conclusions:

    • Targeting specific adenosine and ATP receptors presents promising therapeutic avenues for ischemic stroke.
    • Modulating purinergic signaling offers a dual approach to reduce acute damage and promote long-term brain repair.
    • Further research into purinergic receptor modulation is warranted for effective ischemic stroke treatment.