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Published Online: 6 October 2010

Calcium-Permeable AMPA Receptors Appear in Cortical Neurons after Traumatic Mechanical Injury and Contribute to Neuronal Fate

Publication: Journal of Neurotrauma
Volume 25, Issue Number 10

Abstract

Traumatic brain injury (TBI) is one of the most disabling injuries in the population, with 1.5 million Americans new cases each year and 5.3 million Americans overall requiring long-term daily care as a result of their injuries. One critical aspect in developing effective treatments for TBI is determining if new, specific receptor populations emerge in the early phase after injury that can subsequently be targeted to reduce neuronal death after injury. One specific glutamate receptor subtype, the calcium-permeable AMPA receptor (CP-AMPAR), is becoming increasingly recognized for its role in physiological and pathophysiological processes. Although present in relatively low levels in the mature brain, recent studies show that CP-AMPARs can appear following ischemic brain injury or status epilepticus, and the mechanisms that regulate the appearance of these receptors include alterations in transcription, RNA editing, and receptor trafficking. In this report, we use an in vitro model of TBI to show a gradual appearance of CP-AMPARs four hours following injury to cortical neurons. Moreover, the appearance of these receptors is mediated by the phosphorylation of CaMKIIα following injury. Selectively blocking CP-AMPARs after mechanical injury leads to a significant reduction in the cell death that occurs 24 h following injury in untreated controls, and is similar in protection offered by broad-spectrum NMDA and AMPA receptor antagonists. These data point to a potentially new and more targeted therapeutic approach for treating TBI.

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cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 25Issue Number 10October 2008
Pages: 1207 - 1216
PubMed: 18986222

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Published online: 6 October 2010
Published in print: October 2008

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Jennifer M. Spaethling
Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania.
Donna M. Klein
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.
Pallab Singh
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.
David F. Meaney
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.

Notes

Address reprint requests to:David F. Meaney, Ph.D.Department of Bioengineering240 Skirkanich Hall210 South 33rd StreetPhiladelphia, PA 19104-6321E-mail: [email protected]

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The authors declare that they have no competing financial interests.

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