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Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage

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Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage. / Cisneros-Mejorado, Abraham; Gottlieb, Miroslav; Cavaliere, Fabio; Magnus, Tim; Nolte, Friedrich; Scemes, Eliana; Pérez-Samartín, Alberto; Matute, Carlos.

In: J CEREBR BLOOD F MET, Vol. 35, No. 5, 05.2015, p. 843-50.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Cisneros-Mejorado, A, Gottlieb, M, Cavaliere, F, Magnus, T, Nolte, F, Scemes, E, Pérez-Samartín, A & Matute, C 2015, 'Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage', J CEREBR BLOOD F MET, vol. 35, no. 5, pp. 843-50. https://doi.org/10.1038/jcbfm.2014.262

APA

Cisneros-Mejorado, A., Gottlieb, M., Cavaliere, F., Magnus, T., Nolte, F., Scemes, E., Pérez-Samartín, A., & Matute, C. (2015). Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage. J CEREBR BLOOD F MET, 35(5), 843-50. https://doi.org/10.1038/jcbfm.2014.262

Vancouver

Cisneros-Mejorado A, Gottlieb M, Cavaliere F, Magnus T, Nolte F, Scemes E et al. Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage. J CEREBR BLOOD F MET. 2015 May;35(5):843-50. https://doi.org/10.1038/jcbfm.2014.262

Bibtex

@article{af538759ca09495b93a5eeefe7fe503f,
title = "Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage",
abstract = "The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.",
keywords = "Animals, Brain, Brain Ischemia, Cell Death, Cell Hypoxia, Cells, Cultured, Connexins, Disease Models, Animal, Mice, Mice, Knockout, Nerve Tissue Proteins, Neurons, Purinergic P2X Receptor Antagonists, Rats, Receptors, Purinergic P2X7, Signal Transduction",
author = "Abraham Cisneros-Mejorado and Miroslav Gottlieb and Fabio Cavaliere and Tim Magnus and Friedrich Nolte and Eliana Scemes and Alberto P{\'e}rez-Samart{\'i}n and Carlos Matute",
year = "2015",
month = may,
doi = "10.1038/jcbfm.2014.262",
language = "English",
volume = "35",
pages = "843--50",
journal = "J CEREBR BLOOD F MET",
issn = "0271-678X",
publisher = "SAGE Publications",
number = "5",

}

RIS

TY - JOUR

T1 - Blockade of P2X7 receptors or pannexin-1 channels similarly attenuates postischemic damage

AU - Cisneros-Mejorado, Abraham

AU - Gottlieb, Miroslav

AU - Cavaliere, Fabio

AU - Magnus, Tim

AU - Nolte, Friedrich

AU - Scemes, Eliana

AU - Pérez-Samartín, Alberto

AU - Matute, Carlos

PY - 2015/5

Y1 - 2015/5

N2 - The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.

AB - The role of P2X7 receptors and pannexin-1 channels in ischemic damage remains controversial. Here, we analyzed their contribution to postanoxic depolarization after ischemia in cultured neurons and in brain slices. We observed that pharmacological blockade of P2X7 receptors or pannexin-1 channels delayed the onset of postanoxic currents and reduced their slope, and that simultaneous inhibition did not further enhance the effects of blocking either one. These results were confirmed in acute cortical slices from P2X7 and pannexin-1 knockout mice. Oxygen-glucose deprivation in cortical organotypic cultures caused neuronal death that was reduced with P2X7 and pannexin-1 blockers as well as in organotypic cultures derived from mice lacking P2X7 and pannexin 1. Subsequently, we used transient middle cerebral artery occlusion to monitor the neuroprotective effect of those drugs in vivo. We found that P2X7 and pannexin-1 antagonists, and their ablation in knockout mice, substantially attenuated the motor symptoms and reduced the infarct volume to ~50% of that in vehicle-treated or wild-type animals. These results show that P2X7 receptors and pannexin-1 channels are major mediators of postanoxic depolarization in neurons and of brain damage after ischemia, and that they operate in the same deleterious signaling cascade leading to neuronal and tissue demise.

KW - Animals

KW - Brain

KW - Brain Ischemia

KW - Cell Death

KW - Cell Hypoxia

KW - Cells, Cultured

KW - Connexins

KW - Disease Models, Animal

KW - Mice

KW - Mice, Knockout

KW - Nerve Tissue Proteins

KW - Neurons

KW - Purinergic P2X Receptor Antagonists

KW - Rats

KW - Receptors, Purinergic P2X7

KW - Signal Transduction

U2 - 10.1038/jcbfm.2014.262

DO - 10.1038/jcbfm.2014.262

M3 - SCORING: Journal article

C2 - 25605289

VL - 35

SP - 843

EP - 850

JO - J CEREBR BLOOD F MET

JF - J CEREBR BLOOD F MET

SN - 0271-678X

IS - 5

ER -