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New Strategies in Stroke Intervention pp 175–188Cite as

Role of TRPM7 in Ischemic CNS Injury

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Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

One of the key features noted in animal models of stroke is the progressive nature of the excitotoxic cascade. While the excessive release of glutamate and consequent overactivation of NMDARs occurs rapidly (time span of minutes to hours), the ensuing neuronal death has been noted to progress with some delay, the phenomena being appropriately referred to as delayed neuronal death (DND). Surprisingly, given the massive release of glutamate and strong NMDAR activation, during the early phases of the excitotoxic cascade, neurons are initially capable of regulating and maintaining intracellular Ca2+ near physiological levels. Only with some delay do neurons lose the ability to regulate Ca2+. This delayed rise in intracellular Ca2+ is invariably insensitive to treatment with antiexcitotoxic therapies (AETs), consisting of glutamate receptor and Ca2+ channel blockers [1–3].

The failure of AETs to prevent DND coupled with their inability to provide neuroprotection in clinical trials has led our research groups to seek additional Ca2+ influx pathways in the hopes of identifying previously overlooked sources. Our recent studies have led to the demonstration of the important contribution of TRPM7 channels, the focus of present chapter, to neuronal cell death.

*These authors contributed equally to this work.

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Author information

Authors and Affiliations

  1. Robarts Research Institute, Molecular Brain Research Group, University of Western Ontario, N6A 5K8, London, ON, Canada

    Michael F. Jackson*

  2. Department of Physiology, University of Toronto, King’s College Circle, M5S 1A8, Toronto, ON, Canada

    Hong-Shuo Sun* & Michael Tymianski

  3. Toronto Western Hospital Research Institute, M5T 2S8, Toronto, ON, Canada

    Hong-Shuo Sun* & Michael Tymianski

  4. Robarts Research Institute, University of Western Ontario, 100 Perth Drive, N6A 5K8, London, Ontario, Canada

    John F. MacDonald

Authors
  1. Michael F. Jackson*
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  2. Hong-Shuo Sun*
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  3. Michael Tymianski
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  4. John F. MacDonald
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Corresponding author

Correspondence to John F. MacDonald .

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Editors and Affiliations

  1. Fac. Medicina e Chirurgia, Università di Napoli, Via Sergio Pansini 5, Napoli, 80131, Italy

    Lucio Annunziato

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Jackson*, M.F., Sun*, HS., Tymianski, M., MacDonald, J.F. (2009). Role of TRPM7 in Ischemic CNS Injury. In: Annunziato, L. (eds) New Strategies in Stroke Intervention. Contemporary Neuroscience. Humana Press. https://doi.org/10.1007/978-1-60761-280-3_10

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