Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
May-2018 Volume 17 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2018 Volume 17 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia

  • Authors:
    • Shih‑Huang Tai
    • Wei‑Ting Lee
    • Ai‑Chiang Lee
    • Yu‑Wen Lin
    • Hsin‑Yi Hung
    • Sheng‑Yang Huang
    • Tian‑Shung Wu
    • E‑Jian Lee
  • View Affiliations / Copyright

    Affiliations: Neurophysiology Laboratory, Neurosurgical Service, Department of Surgery, National Cheng Kung University Medical Center and Medical School, Tainan 70428, Taiwan, R.O.C., Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C., School of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C., Institute of Biotechnology, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C.
    Copyright: © Tai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 6490-6496
    |
    Published online on: March 1, 2018
       https://doi.org/10.3892/mmr.2018.8660
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), has been demonstrated to inhibit platelet aggregation, vascular contraction and hypoxia‑inducible factor 1 activity in vitro and in vivo. The present study investigated the neuroprotective efficacy of YC‑1 in cultured neurons exposed to glutamate‑induced excitotoxicity and in an animal model of stroke. In a cortical neuronal culture model, YC‑1 demonstrated neurotoxicity at a concentration >100 µM, and YC‑1 (10‑30 µM) achieved potent cytoprotection against glutamate‑induced neuronal damage. Additionally, YC‑1 (30 µM) effectively attenuated the increase in intracellular Ca2+ levels. Delayed treatment of YC‑1 (30 µM) also protected against glutamate‑induced neuronal damage and cell swelling in cultured neurons, though only at 4 h post‑treatment. In addition, immediate treatment of YC‑1 (30 µM) following the exposure of cortical neurons to glutamate (300 µM) produced a marked reduction in intracellular pH. Delayed treatment of YC‑1 (25 mg/kg) protected against ischemic brain damage in vivo, though only when administered at 3 h post‑insult. Thus, YC‑1 exhibited neuroprotection against glutamate-induced neuronal damage and in mice subjected to transient focal cerebral ischemia. This neuroprotection may be mediated via its ability to limit the glutamate‑induced excitotoxicity. However, the neuroprotective therapeutic window of YC‑1 is only at 3 h in vivo and 4 h in vitro, which may, at least in part, be attributed to its ability to reduce the intracellular pH in the early phase of ischemic stroke. Although YC‑1 provided the potential for clinical therapy, the treatment time point must be carefully evaluated following ischemia.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

O'Bryant Z, Vann KT and Xiong ZG: Translational strategies for neuroprotection in ischemic stroke-focusing on acid-sensing ion channel 1a. Transl Stroke Res. 5:59–68. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Lee EJ, Chen HY, Hung YC, Chen TY, Lee MY, Yu SC, Chen YH, Chuang IC and Wu TS: Therapeutic window for cinnamophilin following oxygen-glucose deprivation and transient focal cerebral ischemia. Exp Neurol. 217:74–83. 2009. View Article : Google Scholar : PubMed/NCBI

3 

Demaerschalk BM and Yip TR: Economic benefit of increasing utilization of intravenous tissue plasminogen activator for acute ischemic stroke in the United States. Stroke. 36:2500–2503. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Xiong ZG, Zhu XM, Chu XP, Minami M, Hey J, Wei WL, MacDonald JF, Wemmie JA, Price MP, Welsh MJ and Simon RP: Neuroprotection in ischemia: Blocking calcium-permeable acid-sensing ion channels. Cell. 118:687–698. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Li MH, Leng TD, Feng XC, Yang T, Simon RP and Xiong ZG: Modulation of acid-sensing ion channel 1a by intracellular pH and its role in ischemic stroke. J Biol Chem. 291:18370–18383. 2016. View Article : Google Scholar : PubMed/NCBI

6 

Mutch WA and Hansen AJ: Extracellular pH changes during spreading depression and cerebral ischemia: Mechanisms of brain pH regulation. J Cereb Blood Flow Metab. 4:17–27. 1984. View Article : Google Scholar : PubMed/NCBI

7 

von Hanwehr R, Smith ML and Siesjö BK: Extra- and intracellular pH during near-complete forebrain ischemia in the rat. J Neurochem. 46:331–339. 1986. View Article : Google Scholar : PubMed/NCBI

8 

Mari Y, Katnik C and Cuevas J: ASIC1a channels are activated by endogenous protons during ischemia and contribute to synergistic potentiation of intracellular Ca(2+) overload during ischemia and acidosis. Cell Calcium. 48:70–82. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Szatkowski M and Attwell D: Triggering and execution of neuronal death in brain ischaemia: Two phases of glutamate release by different mechanisms. Trends Neurosci. 17:359–365. 1994. View Article : Google Scholar : PubMed/NCBI

10 

Dubinsky JM: Intracellular calcium levels during the period of delayed excitotoxicity. J Neurosci. 13:623–631. 1993. View Article : Google Scholar : PubMed/NCBI

11 

Lee WT, Lin MH, Lee EJ, Hung YC, Tai SH, Chen HY, Chen TY and Wu TS: Magnolol reduces glutamate-induced neuronal excitotoxicity and protects against permanent focal cerebral ischemia up to 4 hours. PLoS One. 7:e399522012. View Article : Google Scholar : PubMed/NCBI

12 

Hwang TL, Hung HW, Kao SH, Teng CM, Wu CC and Cheng SJ: Soluble guanylyl cyclase activator YC-1 inhibits human neutrophil functions through a cGMP-independent but cAMP-dependent pathway. Mol Pharmacol. 64:1419–1427. 2003. View Article : Google Scholar : PubMed/NCBI

13 

DeNiro M, Al-Halafi A, Al-Mohanna FH, Alsmadi O and Al-Mohanna FA: Pleiotropic effects of YC-1 selectively inhibit pathological retinal neovascularization and promote physiological revascularization in a mouse model of oxygen-induced retinopathy. Mol Pharmacol. 77:348–367. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Yan J, Zhou B, Taheri S and Shi H: Differential effects of HIF-1 inhibition by YC-1 on the overall outcome and blood-brain barrier damage in a rat model of ischemic stroke. PLoS One. 6:e277982011. View Article : Google Scholar : PubMed/NCBI

15 

Tai SH, Hung YC, Lee EJ, Lee AC, Chen TY, Shen CC, Chen HY, Lee MY, Huang SY and Wu TS: Melatonin protects against transient focal cerebral ischemia in both reproductively active and estrogen-deficient female rats: The impact of circulating estrogen on its hormetic dose-response. J Pineal Res. 50:292–303. 2011. View Article : Google Scholar : PubMed/NCBI

16 

DeLorenzo RJ, Sun DA, Blair RE and Sombati S: An in vitro model of stroke-induced epilepsy: Elucidation of the roles of glutamate and calcium in the induction and maintenance of stroke-induced epileptogenesis. Int Rev Neurobiol. 81:59–84. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Trenholm S and Baldridge WH: The effect of aminosulfonate buffers on the light responses and intracellular pH of goldfish retinal horizontal cells. J Neurochem. 115:102–111. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Tai SH, Chen HY, Lee EJ, Chen TY, Lin HW, Hung YC, Huang SY, Chen YH, Lee WT and Wu TS: Melatonin inhibits postischemic matrix metalloproteinase-9 (MMP-9) activation via dual modulation of plasminogen/plasmin system and endogenous MMP inhibitor in mice subjected to transient focal cerebral ischemia. J Pineal Res. 49:332–341. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Papadia S, Soriano FX, Léveillé F, Martel MA, Dakin KA, Hansen HH, Kaindl A, Sifringer M, Fowler J, Stefovska V, et al: Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses. Nat Neurosci. 11:476–487. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Alzheimer C: Na+ channels and Ca2+ channels of the cell membrane as targets of neuroprotective substances. Adv Exp Med Biol. 513:161–181. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Yang X, Wang Y, Luo J, Liu S and Yang Z: Protective effects of YC-1 against glutamate induced PC12 cell apoptosis. Cell Mol Neurobiol. 31:303–311. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Wang WZ, Chu XP, Li MH, Seeds J, Simon RP and Xiong ZG: Modulation of acid-sensing ion channel currents, acid-induced increase of intracellular Ca2+, and acidosis-mediated neuronal injury by intracellular pH. J Biol Chem. 281:29369–29378. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Jiang N, Wu J, Leng T, Yang T, Zhou Y, Jiang Q, Wang B, Hu Y, Ji YH, Simon RP, et al: Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury. J Cereb Blood Flow Metab. 37:528–540. 2017. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tai SH, Lee WT, Lee AC, Lin YW, Hung HY, Huang SY, Wu TS and Lee EJ: Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia. Mol Med Rep 17: 6490-6496, 2018.
APA
Tai, S., Lee, W., Lee, A., Lin, Y., Hung, H., Huang, S. ... Lee, E. (2018). Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia. Molecular Medicine Reports, 17, 6490-6496. https://doi.org/10.3892/mmr.2018.8660
MLA
Tai, S., Lee, W., Lee, A., Lin, Y., Hung, H., Huang, S., Wu, T., Lee, E."Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia". Molecular Medicine Reports 17.5 (2018): 6490-6496.
Chicago
Tai, S., Lee, W., Lee, A., Lin, Y., Hung, H., Huang, S., Wu, T., Lee, E."Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia". Molecular Medicine Reports 17, no. 5 (2018): 6490-6496. https://doi.org/10.3892/mmr.2018.8660
Copy and paste a formatted citation
x
Spandidos Publications style
Tai SH, Lee WT, Lee AC, Lin YW, Hung HY, Huang SY, Wu TS and Lee EJ: Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia. Mol Med Rep 17: 6490-6496, 2018.
APA
Tai, S., Lee, W., Lee, A., Lin, Y., Hung, H., Huang, S. ... Lee, E. (2018). Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia. Molecular Medicine Reports, 17, 6490-6496. https://doi.org/10.3892/mmr.2018.8660
MLA
Tai, S., Lee, W., Lee, A., Lin, Y., Hung, H., Huang, S., Wu, T., Lee, E."Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia". Molecular Medicine Reports 17.5 (2018): 6490-6496.
Chicago
Tai, S., Lee, W., Lee, A., Lin, Y., Hung, H., Huang, S., Wu, T., Lee, E."Therapeutic window for YC‑1 following glutamate‑induced neuronal damage and transient focal cerebral ischemia". Molecular Medicine Reports 17, no. 5 (2018): 6490-6496. https://doi.org/10.3892/mmr.2018.8660
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team