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Protection from Glutamate-Induced Excitotoxicity by Memantine

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Abstract

This study investigates whether the uncompetitive N-methyl-d-aspartic acid receptor antagonist, memantine, is able to protect dissociated cortical neurons from glutamate-induced excitotoxicity (GIE). Treatment with glutamate resulted in a significant loss of synchronization of neuronal activity as well as a significant increase in the duration of synchronized bursting events (SBEs). By administering memantine at the same time as glutamate, we were able to completely prevent these changes to the neuronal activity. Pretreatment with memantine was somewhat effective in preventing changes to the culture synchronization but was unable to fully protect the synchronization of electrical activity between neurons that showed high levels of synchronization prior to injury. Additionally, memantine pretreatment was unable to prevent the increase in the duration of SBEs caused by GIE. Thus, the timing of memantine treatment is important for conferring neuroprotection against glutamate-induced neurotoxicity. Finally, we found that GIE leads to a significant increase in the burst duration. Our data suggest that this may be due to an alteration in the inhibitory function of the neurons.

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Acknowledgments

This work was funded by a grant from the New Jersey Commission on Brain Injury Research, #09-3209-BIR-E-2 to BLF. MLK was supported by Biotechnology Fellowship, Grant 5T32GM008339 from National Institute of General Medical Sciences.

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Authors and Affiliations

  1. Department of Cell Biology and Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ, 08854-8082, USA

    Melinda K. Kutzing, Vincent Luo & Bonnie L. Firestein

  2. Graduate Program in Biomedical Engineering, Rutgers University, 604 Allison Road, Piscataway, NJ, 08854-8082, USA

    Melinda K. Kutzing

  3. Department of Biomedical Engineering, Rutgers University, 604 Allison Road, Piscataway, NJ, 08854-8082, USA

    Bonnie L. Firestein

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  1. Melinda K. Kutzing
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  2. Vincent Luo
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  3. Bonnie L. Firestein
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Correspondence to Bonnie L. Firestein.

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Associate Editor Berj L. Bardakjian oversaw the review of this article.

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Kutzing, M.K., Luo, V. & Firestein, B.L. Protection from Glutamate-Induced Excitotoxicity by Memantine. Ann Biomed Eng 40, 1170–1181 (2012). https://doi.org/10.1007/s10439-011-0494-z

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  • DOI: https://doi.org/10.1007/s10439-011-0494-z

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