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Sexually Dimorphic Response of TRPM2 Inhibition Following Cardiac Arrest-Induced Global Cerebral Ischemia in Mice

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Abstract

Transient global cerebral ischemia due to cardiac arrest followed by resuscitation (CA/CPR) causes significant neurological damage in vulnerable neuron populations within the brain, such as hippocampal CA1 neurons. In recent years, we have implicated the transient receptor potential M2 (TRPM2) channel as a mediator of ischemic injury to neurons. We previously demonstrated that genetic and pharmacological strategies that reduce TRPM2 function preferentially protect male neurons in vitro and reduce infarct volume following experimental stroke. Due to the narrow therapeutic window for intervention following ischemic stroke, it is important to assess the role of TRPM2 in other models of cerebral ischemia. Therefore, this study utilized a modified mouse model of CA/CPR to mimic more accurately the clinical condition by maintaining body and head temperatures near the physiological range throughout. Here, we report that inhibition of TRPM2 activity with clotrimazole reduces hippocampal CA1 neuronal injury when administered 30 min after resuscitation from cardiac arrest. Consistent with our previous observations, neuroprotection was observed in male mice and no effect on injury was observed in the female. These findings provide further evidence for TRPM2 as a target for protection against cerebral ischemia in the male brain.

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Acknowledgments

This work supported in part by R01NS058792 and the Walter S. and Lucienne Driskill Foundation Award.

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Authors and Affiliations

  1. Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, OR, USA

    S. Nakayama

  2. Department of Pharmacology, University of Colorado School of Medicine, Anschutz Medical Campus, 12800 E. 19th Ave, Aurora, CO, 80045, USA

    R. J. Traystman & P. S. Herson

  3. Department of Anesthesiology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave, Aurora, CO, 80045, USA

    R. Vest, R. J. Traystman & P. S. Herson

  4. Department of Pharmacology, University of Colorado Denver, Anschutz Medical Campus, 12800 E. 19th Ave, Aurora, CO, 80045, USA

    R. J. Traystman & P. S. Herson

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  1. S. Nakayama
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  2. R. Vest
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  3. R. J. Traystman
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  4. P. S. Herson
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Correspondence to P. S. Herson.

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Nakayama, S., Vest, R., Traystman, R.J. et al. Sexually Dimorphic Response of TRPM2 Inhibition Following Cardiac Arrest-Induced Global Cerebral Ischemia in Mice. J Mol Neurosci 51, 92–98 (2013). https://doi.org/10.1007/s12031-013-0005-9

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  • DOI: https://doi.org/10.1007/s12031-013-0005-9

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