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

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

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.

Keywords

Cerebral Ischemia Middle Cerebral Artery Occlusion Intracellular Acidosis Mouse Middle Cerebral Artery Occlusion Mouse Middle Cerebral Artery Occlusion Model 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

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

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Neuroscience Training ProgramUniversity of WisconsinMadisonUSA
  2. 2.Department of NeurologyUniversity of PittsburghPittsburghUSA
  3. 3.Department of Neurological SurgeryUniversity of WisconsinMadisonUSA

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