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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
October 2014 Volume 8 Issue 4

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
October 2014 Volume 8 Issue 4

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

Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway

  • Authors:
    • Xiaojuan Li
    • Junhe Zhang
    • Shujie Chai
    • Xiaoyin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Department of Biochemistry and Molecular Biology, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China
  • Pages: 1241-1246
    |
    Published online on: July 21, 2014
       https://doi.org/10.3892/etm.2014.1858
  • 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

This aim of this study was to investigate whether progesterone (PROG) alleviates the neuronal apoptosis in neonatal rats with hypoxic‑ischemic (HI) brain damage through the phosphatidylinositol 3‑kinase (PI3K)/Akt/glycogen synthase kinase‑3β (GSK‑3β) signaling pathway. A total of 96 newborn Wistar rats aged 7 days were randomly divided into four groups: sham surgery, HI, drug prevention (PROG) and Akt inhibitor groups. HI animal models were established by a conventional method. All animals were sacrificed 24 h after hypoxia. Immunohistochemistry was used to detect the distribution and expression of phosphorylated Akt (p‑Akt) and the GSK‑3β proteins in the brain, and western blot analysis was used to determine the p‑Akt and GSK‑3β protein contents. An enzyme‑linked immunosorbent assay was also used to determine the GSK‑3β content of the brain tissue, and flow cytometry was used to evaluate the apoptosis rate of neural cells. The expression of p‑Akt protein was reduced in the brain tissues of the HI group, whereas GSK‑3β expression was increased. In addition, the GSK‑3β content of the brain and the neuronal apoptosis rate were significantly increased. PROG pre‑treatment increased p‑Akt expression, decreased GSK‑3β expression and GSK‑3β content, and also reduced neuronal apoptosis. Following administration of the Akt inhibitor wortmannin, p‑Akt expression decreased, GSK‑3β expression increased, and the GSK‑3β content and neuronal apoptosis rate significantly increased (P<0.05). In conclusion, PROG activates the PI3K/Akt/GSK‑3β pathway to promote Akt activation, enhance p‑Akt expression and inhibit GSK‑3β expression, thereby inhibiting neuronal apoptosis, alleviating HI brain injury and inducing a cerebroprotective effect.
View Figures

Figure 1

Figure 2

View References

1 

Liu F and McCullough LD: Inflammatory responses in hypoxic ischemic encephalopathy. Acta Pharmacol Sin. 34:1121–1130. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Kasdorf E and Perlman JM: Hyperthermia, inflammation, and perinatal brain injury. Pediatr Neurol. 49:8–14. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Gu Q, Zhai L, Feng X, et al: Apelin-36, a potent peptide, protects against ischemic brain injury by activating the PI3K/Akt pathway. Neurochem Int. 63:535–540. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Zhang B, Ji X, Zhang S, Ren H, Wang M, Guo C and Li Y: Hemin-mediated neuroglobin induction exerts neuroprotection following ischemic brain injury through PI3K/Akt signaling. Mol Med Rep. 8:681–685. 2013.

5 

Xiong T, Tang J, Zhao J, et al: Involvement of the Akt/GSK-3β/CRMP-2 pathway in axonal injury after hypoxic-ischemic brain damage in neonatal rat. Neuroscience. 216:123–132. 2012.

6 

Valerio A, Bertolotti P, Delbarba A, et al: Glycogen synthase kinase-3 inhibition reduces ischemic cerebral damage, restores impaired mitochondrial biogenesis and prevents ROS production. J Neurochem. 116:1148–1159. 2011. View Article : Google Scholar

7 

Singh M and Su C: Progesterone-induced neuroprotection: factors that may predict therapeutic efficacy. Brain Res. 1514:98–106. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Baudry M, Bi X and Aguirre C: Progesterone-estrogen interactions in synaptic plasticity and neuroprotection. Neuroscience. 239:280–294. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Wang X, Zhang J, Yang Y, Dong W, Wang F, Wang L and Li X: Progesterone attenuates cerebral edema in neonatal rats with hypoxic-ischemic brain damage by inhibiting the expression of matrix metalloproteinase-9 and aquaporin-4. Exp Ther Med. 6:263–267. 2013.PubMed/NCBI

10 

Sarkaki AR, Khaksari Haddad M, Soltani Z, Shahrokhi N and Mahmoodi M: Time- and dose-dependent neuroprotective effects of sex steroid hormones on inflammatory cytokines after a traumatic brain injury. J Neurotrauma. 30:47–54. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Tsuji M, Taguchi A, Ohshima M, Kasahara Y and Ikeda T: Progesterone and allopregnanolone exacerbate hypoxic-ischemic brain injury in immature rats. Exp Neurol. 233:214–20. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Shahrokhi N, Khaksari M, Soltani Z, Mahmoodi M and Nakhaee N: Effect of sex steroid hormones on brain edema, intracranial pressure, and neurologic outcomes after traumatic brain injury. Can J Physiol Pharmacol. 88:414–421. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Taniguchi H and Andreasson K: The hypoxic-ischemic encephalopathy model of perinatal ischemia. J Vis Exp. 19:3791–3792. 2008.

14 

Doi K, Sameshima H, Kodama Y, Furukawa S, Kaneko M and Ikenoue TK: Perinatal death and neurological damage as a sequential chain of poor outcome. J Matern Fetal Neonatal Med. 25:706–709. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Northington FJ, Chavez-Valdez R and Martin LJ: Neuronal cell death in neonatal hypoxia-ischemia. Ann Neurol. 69:743–758. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Zhu YM, Wang CC, Chen L, et al: Both PI3K/Akt and ERK1/2 pathways participate in the protection by dexmedetomidine against transient focal cerebral ischemia/reperfusion injury in rats. Brain Res. 494:1–8. 2013. View Article : Google Scholar

17 

Zhang X, Zhang X, Wang C, et al: Neuroprotection of early and short-time applying berberine in the acute phase of cerebral ischemia: up-regulated pAkt, pGSK and pCREB, down-regulated NF-κB expression, ameliorated BBB permeability. Brain Res. 1459:61–70. 2012.PubMed/NCBI

18 

Zhou C, Tu J, Zhang Q, et al: Delayed ischemic postconditioning protects hippocampal CA1 neurons by preserving mitochondrial integrity via Akt/GSK3β signaling. Neurochem Int. 59:749–758. 2011.PubMed/NCBI

19 

Sun B, Chen L, Wei X, Xiang Y, Liu X and Zhang X: The Akt/GSK-3β pathway mediates flurbiprofen-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rats. Biochem Biophys Res Commun. 409:808–813. 2011.

20 

Collino M, Aragno M, Castiglia S, Tomasinelli C, Thiemermann C, Boccuzzi G and Fantozzi R: Insulin reduces cerebral ischemia/reperfusion injury in the hippocampus of diabetic rats: a role for glycogen synthase kinase-3beta. Diabetes. 58:235–242. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Wang XY, Li XJ, Li DL, Li XJ, Zhu XQ and Guo XP: Neuroprotective effect of progesterone in newborn rats with hypoxic-ischemic encephalopathy. Int J Phys Sci. 6:2894–2900. 2011.

22 

Zhao H, Shimohata T, Wang JQ, Sun G, Schaal DW, Sapolsky RM and Steinberg GK: Akt contributes to neuroprotection by hypothermia against cerebral ischemia in rats. J Neurosci. 25:9794–9806. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Endo H, Nito C, Kamada H, Nishi T and Chan PH: Activation of the Akt/GSK3beta signaling pathway mediates survival of vulnerable hippocampal neurons after transient global cerebral ischemia in rats. J Cereb Blood Flow Metab. 26:1479–1489. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Li L, Qu Y, Mao M, Xiong Y and Mu D: The involvement of phosphoinositide 3-kinase/Akt pathway in the activation of hypoxia-inducible factor-1alpha in the developing rat brain after hypoxia-ischemia. Brain Res. 1197:152–158. 2008. View Article : Google Scholar : PubMed/NCBI

25 

Yao D, He X, Wang JH and Zhao ZY: Effects of PI3K/Akt signaling pathway on learning and memory abilities in neonatal rats with hypoxic-ischemic brain damage. Zhongguo Dang Dai Er Ke Za Zhi. 13:424–427. 2011.(In Chinese).

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li X, Zhang J, Chai S and Wang X: Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway. Exp Ther Med 8: 1241-1246, 2014.
APA
Li, X., Zhang, J., Chai, S., & Wang, X. (2014). Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway. Experimental and Therapeutic Medicine, 8, 1241-1246. https://doi.org/10.3892/etm.2014.1858
MLA
Li, X., Zhang, J., Chai, S., Wang, X."Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway". Experimental and Therapeutic Medicine 8.4 (2014): 1241-1246.
Chicago
Li, X., Zhang, J., Chai, S., Wang, X."Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway". Experimental and Therapeutic Medicine 8, no. 4 (2014): 1241-1246. https://doi.org/10.3892/etm.2014.1858
Copy and paste a formatted citation
x
Spandidos Publications style
Li X, Zhang J, Chai S and Wang X: Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway. Exp Ther Med 8: 1241-1246, 2014.
APA
Li, X., Zhang, J., Chai, S., & Wang, X. (2014). Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway. Experimental and Therapeutic Medicine, 8, 1241-1246. https://doi.org/10.3892/etm.2014.1858
MLA
Li, X., Zhang, J., Chai, S., Wang, X."Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway". Experimental and Therapeutic Medicine 8.4 (2014): 1241-1246.
Chicago
Li, X., Zhang, J., Chai, S., Wang, X."Progesterone alleviates hypoxic‑ischemic brain injury via the Akt/GSK‑3β signaling pathway". Experimental and Therapeutic Medicine 8, no. 4 (2014): 1241-1246. https://doi.org/10.3892/etm.2014.1858
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