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Dantrolene: Mechanisms of Neuroprotection and Possible Clinical Applications in the Neurointensive Care Unit

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Abstract

Calcium plays a central role in neuronal function and injury. Dantrolene, an inhibitor of the ryanodine receptor, inhibits intracellular calcium release from the sarco-endoplasmic reticulum. We review the available data of dantrolene as a potential neuroprotective agent and briefly summarize its other pharmacologic effects that may have potential applications for patients in the neurointensive care unit (NICU). Areas with the need for continued research are identified.

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Abbreviations

ADP:

Adenosine diphosphate

AMPA:

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ATP:

Adenosine triphosphate

CaM:

Calmodulin

CICR:

Calcium-induced calcium release

CytC:

Cytochrome C

DNA:

Deoxyribonucleic acid

KA:

Kainic acid

MtPTP:

Mitochondrial permeability transition pore

NAD:

Nicotinamide adenine dinucleotide

NMDA:

N-methyl-D-aspartic acid

NO:

Nitric oxide

NOS:

Nitric oxide synthase

PARP:

Poly (ADP-ribose) polymerase

RyR:

Ryanodine receptor

SERCA:

Sarco-endoplasmic reticulum Ca2+-ATPase

UPR:

Unfolded protein response

VGCC:

Voltage gated calcium channel

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Acknowledgment

Dr. John R. Sims is supported by NIH 1 K08 NS049241-01A2. We would like to thank Susanne L. Loomis for help in preparing Fig. 1.

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Authors and Affiliations

  1. Departments of Neurology, Anesthesiology/Critical Care and Surgery, UMASS Memorial Medical Center, University Campus, University of Massachusetts Medical School, Worcester, MA, 01605, USA

    Susanne Muehlschlegel

  2. Department of Neurology, Division of Neurocritical Care and Acute Stroke, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA

    John R. Sims

  3. Department of Radiology, Massachusetts General Hospital, Harvard Medical School, CNY149 Rm6403, 13th Street, Charlestown, Boston, MA, 02129, USA

    John R. Sims

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  1. Susanne Muehlschlegel
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Correspondence to John R. Sims.

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Muehlschlegel, S., Sims, J.R. Dantrolene: Mechanisms of Neuroprotection and Possible Clinical Applications in the Neurointensive Care Unit. Neurocrit Care 10, 103–115 (2009). https://doi.org/10.1007/s12028-008-9133-4

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  • DOI: https://doi.org/10.1007/s12028-008-9133-4

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