NMDA receptor activation contributes to a portion of the decreased mitochondrial membrane potential and elevated intracellular free calcium in strain-injured neurons

    Authors

    S. M. Ahmed; J. T. Weber; S. Liang; K. A. Willoughby; H. A. Sitterding; B. A. Rzigalinski;E. F. Ellis

    Comments

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    Abbreviated Journal Title

    J. Neurotrauma

    Keywords

    APV; calcium; glutamate; mitochondria; MK-801; traumatic brain injury; STRETCH-INDUCED INJURY; ENERGY-METABOLISM; CORTICAL-NEURONS; BRAIN; INJURY; IN-VITRO; GLUTAMATE EXCITOTOXICITY; DELAYED DEPOLARIZATION; SIGNAL-TRANSDUCTION; HEAD-INJURY; CELL INJURY; Critical Care Medicine; Clinical Neurology; Neurosciences

    Abstract

    In our previous studies, we have shown that in vitro biaxial strain (stretch) injury of neurons in neuronal plus glial cultures increases intracellular free calcium ([Ca2+](i)) and decreases mitochondrial membrane potential (Deltapsi(m)). The goal of this study was to determine whether strain injury, without the addition of exogenous agents, causes glutamate release, and whether NMDA receptor antagonists affect the post-strain injury rise in [Ca2+](i) and decrease in Deltapsi(m). [Ca2+](i) and Deltapsi(m). were measured using the fluorescent indicators fura-2 AM and rhodamine-1,2,3 (rh123). Strain injury of neuronal plus glial cultures caused an immediate 100-200 nM elevation in neuronal [Ca2+](i) and a decline in neuronal Deltapsi(m) by 15 min post-injury. Pretreatment with the NMDA receptor antagonist MK-801 (10 muM) attenuated the [Ca2+](i) elevation after mild, but not moderate and severe injury. MK-801 pretreatment reduced the decline in Deltapsi(m) after mild and moderate, but not after severe injury. The NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid (APV; 100 muM) had effects similar to MK-801. Simultaneous measurement of [Ca2+](i) and Deltapsi(m). demonstrated a significant correlation and a temporal relationship between [Ca2+](i) elevation and depression of Deltapsi(m). We conclude that NMDA receptor stimulation contributes to some of the changes in [Ca2+](i) and Deltapsi(m) after less severe strain injury. However, after more pronounced injury other mechanisms appear to be more involved.

    Journal Title

    Journal of Neurotrauma

    Volume

    19

    Issue/Number

    12

    Publication Date

    1-1-2002

    Document Type

    Article

    Language

    English

    First Page

    1619

    Last Page

    1629

    WOS Identifier

    WOS:000180070700009

    ISSN

    0897-7151

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