Evidence map›Paper›PMID 16339021›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005

Decreased neuronal death in Na+/H+ exchanger isoform 1-null mice after in vitro and in vivo ischemia.

Jing Luo, Hai Chen, Douglas B Kintner, Gary E Shull, Dandan Sun

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 115 citations in OpenAlex.

  1. Article
  2. Article
  3. A dangerous liaison: Spreading depolarization and tissue acidification in cerebral ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025
    Review
  4. Review
  5. The Systemic Administration of NaJournal of clinical practice and research · 2024
    Article
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  7. Review
  8. Article
  9. Role of NaJournal of molecular medicine (Berlin, Germany) · 2022
    Review
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  12. Article
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  14. Article
  15. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Jing LuoDepartment of Physiology, University of Wisconsin Medical School, Madison, Wisconsin 53792, USA.
Hai Chen
Douglas B Kintner
Gary E Shull
Dandan Sun
University of Wisconsin–Madison · USUniversity of Cincinnati · US

Funding

The Role of Na+/H+ exchanger in Cerebral IschemiaR01NS048216 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI Dandan Sun · 2005 to 2026
$6.1M
Mouse Models for Ion Homeostasis Defects in HeartR01HL061974 · NHLBI · UNIVERSITY OF CINCINNATI · PI SHULL, GARY EDWARD · 1999 to 2010
$5.1M
Na-K-Cl Contransporter in Cerebral IschemiaR01NS038118 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI SUN, DANDAN · 2000 to 2018
$5.0M
NHLBI NIH HHS R01 HL061974NHLBI NIH HHS R01HL61974NINDS NIH HHS R01 NS038118NINDS NIH HHS R01 NS048216NINDS NIH HHS R01NS048216NINDS NIH HHS R01NS38118
6 · The paper itself

Abstract

Na+/H+ exchanger isoform 1 (NHE1) is a major acid extrusion mechanism after intracellular acidosis. We hypothesized that stimulation of NHE1 after cerebral ischemia contributes to the disruption of Na+ homeostasis and neuronal death. In the present study, expression of NHE1 was detected in cultured mouse cortical neurons. Three hours of oxygen and glucose deprivation (OGD) followed by 21 h of reoxygenation (REOX) led to 68 +/- 10% cell death. Inhibition of NHE1 with the potent inhibitor cariporide (HOE 642) or genetic ablation of NHE1 reduced OGD-induced cell death by approximately 40-50% (p < 0.05). In NHE1(+/+) neurons, OGD caused a twofold increase in [Na+]i, and 60 min REOX triggered a sevenfold increase. Genetic ablation of NHE1 or HOE 642 treatment had no effects on the OGD-mediated initial Na+(i) rise but reduced the second phase of Na+(i) rise by approximately 40-50%. In addition, 60 min REOX evoked a 1.5-fold increase in [Ca2+]i in NHE1(+/+) neurons, which was abolished by inhibition of either NHE1 or reverse-mode operation of Na+/Ca2+ exchange. OGD/REOX-mediated mitochondrial Ca2+ accumulation and cytochrome c release were attenuated by inhibition of NHE1 activity. In an in vivo focal ischemic model, 2 h of left middle cerebral artery occlusion followed by 24 h of reperfusion induced 84.8 +/- 8.0 mm3 infarction in NHE1(+/+) mice. NHE1(+/+) mice treated with HOE 642 or NHE1 heterozygous mice exhibited a approximately 33% decrease in infarct size (p < 0.05). These results imply that NHE1 activity disrupts Na+ and Ca2+ homeostasis and contributes to ischemic neuronal damage.

Indexed as

AnimalsBrain IschemiaCation Transport ProteinsCell DeathCell HypoxiaCells, CulturedEnzyme ActivationFemaleMaleMembrane ProteinsMiceMice, KnockoutNeuronsPregnancySodium-Hydrogen Exchanger 1Sodium-Hydrogen ExchangersCation Transport ProteinsMembrane ProteinsSlc9a1 protein, mouseSodium-Hydrogen Exchanger 1Sodium-Hydrogen Exchangers

Identifiers

PMID16339021
PMCPMC6725894
OpenAlexW2094114130

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.