Neuroprotective Strategies: Voltage-Gated Na+-Channel Down-Modulation versus Presynaptic Glutamate Release Inhibition

Neuroprotective Strategies: Voltage-Gated Na+-Channel Down-Modulation versus Presynaptic... ©Freund & Pettman, U.K. , 9, 203-211 (1998) Tihomir P. Obrenovitch Postgraduate Studies in Pharmacology, School of Pharmacy University of Bradford, Bradford, BD7 J DP, UK SYNOPSIS 1. INTRODUCTION Insufficient ATP production relative to cellular requirements is the key factor detrimental to neurons in neurological disorders associated with deficient oxygen/glucose supply or mitochondrial dysfunction. As a large part of the energy consumed by brain cells is used to maintain the Na+ gradient across the cellular membrane, reduction of energy demand by down-modulation of voltage-gated Na + -channels is a rational strategy for neuroprotection against these conditions. Preservation of the inward Na+ gradient is likely to be also beneficial as it is an essential driving force for vital ion exchanges and transport mechanisms (e.g. Ca 2+ -homeostasis and cell volume regulation). From these elements, I propose that use-dependent Na + channel blockers increase the resilience of nerve cells to the primary insult and/or subsequent deleterious events, and that reduced efflux of glutamate and other compounds is only a consequence of cellular stress attenuation. The widespread hypothesis that down-modulation of Na + -channels is neuroprotective primarily through reduction of presynaptic glutamate release conflicts with strong experimental evidence. KEY WORDS neuroprotection, http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Reviews in the Neurosciences de Gruyter

Neuroprotective Strategies: Voltage-Gated Na+-Channel Down-Modulation versus Presynaptic Glutamate Release Inhibition

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Publisher
de Gruyter
Copyright
Copyright © 1998 by the
ISSN
2191-0200
eISSN
2191-0200
D.O.I.
10.1515/REVNEURO.1998.9.3.203
Publisher site
See Article on Publisher Site

Abstract

©Freund & Pettman, U.K. , 9, 203-211 (1998) Tihomir P. Obrenovitch Postgraduate Studies in Pharmacology, School of Pharmacy University of Bradford, Bradford, BD7 J DP, UK SYNOPSIS 1. INTRODUCTION Insufficient ATP production relative to cellular requirements is the key factor detrimental to neurons in neurological disorders associated with deficient oxygen/glucose supply or mitochondrial dysfunction. As a large part of the energy consumed by brain cells is used to maintain the Na+ gradient across the cellular membrane, reduction of energy demand by down-modulation of voltage-gated Na + -channels is a rational strategy for neuroprotection against these conditions. Preservation of the inward Na+ gradient is likely to be also beneficial as it is an essential driving force for vital ion exchanges and transport mechanisms (e.g. Ca 2+ -homeostasis and cell volume regulation). From these elements, I propose that use-dependent Na + channel blockers increase the resilience of nerve cells to the primary insult and/or subsequent deleterious events, and that reduced efflux of glutamate and other compounds is only a consequence of cellular stress attenuation. The widespread hypothesis that down-modulation of Na + -channels is neuroprotective primarily through reduction of presynaptic glutamate release conflicts with strong experimental evidence. KEY WORDS neuroprotection,

Journal

Reviews in the Neurosciencesde Gruyter

Published: Jul 1, 1998

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