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Na+/H+ Exchangers as Therapeutic Targets for Cerebral Ischemia

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Translational Stroke Research

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

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Abstract

The Na+/H+ exchangers (NHE) are a family of membrane transporters that catalyzes the exchange of intracellular H+ with extracellular Na+ and plays a role in regulating intracellular pH and cell volume. Following cerebral ischemia, the “housekeeping” NHE isoform 1 (NHE-1) is stimulated by intracellular acidosis to remove excess H+. Overstimulation of NHE-1 causes accumulation of Na+ and Ca2+ inside the cell through the reversal mode of Na+/Ca2+ exchange (NCX) and eventually contributes to cell death. Pharmacological inhibition or genetic knockdown of NHE-1 is neuroprotective in both in vitro and in vivo ischemia models as shown by reduced neuronal death and blockade of intracellular Ca2+ and Na+ accumulation. Inhibition of NHE-1 not only reduces brain infarct volume but also improves long-term neurological functions. Inhibition of NHE-1 also has a profound effect on neuroinflammation and edema formation, providing a longer treatment time window for stroke therapy. Therefore, NHE-1 merges as an important target for developing new therapeutics for stroke treatment.

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Acknowledgments

This work was supported by NIH grants R01NS 48216 and R01NS 38118 (D. Sun).

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Authors and Affiliations

  1. Neuroscience Training Program, University of Wisconsin, Madison, WI, 53705, USA

    Yejie Shi & Dandan Sun MD, PhD

  2. Department of Neurology, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Yejie Shi & Dandan Sun MD, PhD

  3. Department of Neurological Surgery, University of Wisconsin, Madison, WI, 53705, USA

    Dandan Sun MD, PhD

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  1. Yejie Shi
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Correspondence to Dandan Sun MD, PhD .

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Editors and Affiliations

  1. , Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, 90048, California, USA

    Paul A. Lapchak

  2. Loma Linda University, 11234 Anderson Street, Room 2562B, Loma Linda, 92354, California, USA

    John H. Zhang

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Shi, Y., Sun, D. (2012). Na+/H+ Exchangers as Therapeutic Targets for Cerebral Ischemia. In: Lapchak, P., Zhang, J. (eds) Translational Stroke Research. Springer Series in Translational Stroke Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9530-8_20

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