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Updated: Aug 11, 2026
2-Vessel Occlusion/Hypotension: A Rat Model of Global Brain Ischemia
Published on: June 22, 2013
Censoring the editor in transient forebrain ischemia
1Department of Physiology, University College London, London WC1E 6BT, United Kingdom.
Abstract:
A molecular explanation for why some neurons are more vulnerable than others to ischemic injury has long remained elusive. In this issue of Neuron, Peng et al. propose that CREB-dependent downregulation of the RNA editing enzyme ADAR2, resulting in defective Q/R editing of AMPA receptor GluR2 subunits and increased availability of calcium and zinc-permeable death-promoting AMPA receptors, underlies the vulnerability of some neuronal populations to ischemia.
Insights
Vulnerability to ischemic injury in neurons is explained by CREB-mediated reduction of ADAR2. This leads to faulty AMPA receptor editing, increasing cell death.
Area of Science:
- Neuroscience
- Molecular Biology
- Cellular Biology
Background:
- Neuronal vulnerability to ischemic injury lacks a clear molecular basis.
- Specific neuronal populations exhibit differential susceptibility to stroke-related damage.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying differential neuronal vulnerability to ischemic injury.
- To identify key molecular players involved in neuronal cell death during ischemia.
Main Methods:
- Investigated the role of CREB (cAMP response element-binding protein) in regulating gene expression during ischemia.
- Assessed the impact of CREB on the RNA editing enzyme ADAR2 (adenosine deaminase acting on RNA 2).
- Analyzed the Q/R editing status of AMPA receptor GluR2 subunits and its correlation with neuronal survival.
Main Results:
- CREB-dependent downregulation of ADAR2 was identified as a critical factor in neuronal vulnerability.
- Defective Q/R editing of AMPA receptor GluR2 subunits was observed in vulnerable neurons.
- Increased availability of calcium and zinc-permeable AMPA receptors contributes to excitotoxicity and cell death.
Conclusions:
- CREB-mediated downregulation of ADAR2 explains neuronal susceptibility to ischemic damage.
- Targeting ADAR2 or AMPA receptor editing may offer therapeutic strategies for stroke.
- Understanding these molecular pathways is crucial for developing neuroprotective treatments.
