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
June-2016 Volume 11 Issue 6

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
June-2016 Volume 11 Issue 6

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

Effects of melatonin on cognitive impairment and hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion

  • Authors:
    • Choong Hyun Lee
    • Joon Ha Park
    • Ji Hyeon Ahn
    • Moo‑Ho Won
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan, Chungcheongnam 330‑714, Republic of Korea, Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 200‑701, Republic of Korea
    Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2240-2246
    |
    Published online on: April 1, 2016
       https://doi.org/10.3892/etm.2016.3216
  • 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

Chronic cerebral hypoperfusion (CCH), which induces oxidative stress and inflammation in the brain, has previously been associated with cognitive impairment and neuronal cell damage. Melatonin is a well-known free radical scavenger and antioxidant; therefore, the present study investigated the protective effects of melatonin against CCH‑induced cognitive impairment and neuronal cell death in a CCH rat model, which was generated via permanent bilateral common carotid artery occlusion (2VO). The rats in the 2VO group exhibited markedly increased escape latencies in a Morris water maze test, as compared with the rats in the sham group. In addition, increased neuronal cell damage was detected in the hippocampal CA1 region of the 2VO rats, as compared with the rats in the sham group. Treatment of the 2VO rats with melatonin significantly reduced the escape latency and neuronal cell damage, and was associated with reduced levels of malondialdehyde, microglial activation, and tumor necrosis factor‑α and interleukin‑1β in the ischemic hippocampus. The results of the present study suggest that melatonin may attenuate CCH‑induced cognitive impairment and hippocampal neuronal cell damage by decreasing oxidative stress, microglial activation and the production of pro-inflammatory cytokines in the ischemic hippocampus.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Farkas E, Luiten PG and Bari F: Permanent, bilateral common carotid artery occlusion in the rat: A model for chronic cerebral hypoperfusion-related neurodegenerative diseases. Brain Res Rev. 54:162–180. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Román GC: Brain hypoperfusion: A critical factor in vascular dementia. Neurol Res. 26:454–458. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Farkas E, Donka G, de Vos RA, Mihály A, Bari F and Luiten PG: Experimental cerebral hypoperfusion induces white matter injury and microglial activation in the rat brain. Acta Neuropathol. 108:57–64. 2004. View Article : Google Scholar : PubMed/NCBI

4 

He XL, Wang YH, Bi MG and Du GH: Chrysin improves cognitive deficits and brain damage induced by chronic cerebral hypoperfusion in rats. Eur J Pharmacol. 680:41–48. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Kasparová S, Brezová V, Valko M, Horecký J, Mlynárik V, Liptaj T, Vancová O, Ulicná O and Dobrota D: Study of the oxidative stress in a rat model of chronic brain hypoperfusion. Neurochem Int. 46:601–611. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Ozacmak VH, Barut F and Ozacmak HS: Melatonin provides neuroprotection by reducing oxidative stress and HSP70 expression during chronic cerebral hypoperfusion in ovariectomized rats. J Pineal Res. 47:156–163. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Xi Y, Wang M, Zhang W, Bai M, Du Y, Zhang Z, Li Z and Miao J: Neuronal damage, central cholinergic dysfunction and oxidative damage correlate with cognitive deficits in rats with chronic cerebral hypoperfusion. Neurobiol Learn Mem. 109:7–19. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Cechetti F, Pagnussat AS, Worm PV, Elsner VR, Ben J, da Costa MS, Mestriner R, Weis SN and Netto CA: Chronic brain hypoperfusion causes early glial activation and neuronal death, and subsequent long-term memory impairment. Brain Res Bull. 87:109–116. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Feng Z, Lu Y, Wu X, Zhao P, Li J, Peng B, Qian Z and Zhu L: Ligustilide alleviates brain damage and improves cognitive function in rats of chronic cerebral hypoperfusion. J Ethnopharmacol. 144:313–321. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Lee CH, Yoo KY, Choi JH, Park OK, Hwang IK, Kwon YG, Kim YM and Won MH: Melatonin's protective action against ischemic neuronal damage is associated with up-regulation of the MT2 melatonin receptor. J Neurosci Res. 88:2630–2640. 2010.PubMed/NCBI

11 

Zhu B, Wang ZG, Ding J, Liu N, Wang DM, Ding LC and Yang C: Chronic lipopolysaccharide exposure induces cognitive dysfunction without affecting BDNF expression in the rat hippocampus. Exp Ther Med. 7:750–754. 2014.PubMed/NCBI

12 

De Jong GI, Farkas E, Stienstra CM, Plass JR, Keijser JN, de la Torre JC and Luiten PG: Cerebral hypoperfusion yields capillary damage in the hippocampal CA1 area that correlates with spatial memory impairment. Neuroscience. 91:203–210. 1999. View Article : Google Scholar : PubMed/NCBI

13 

Sarti C, Pantoni L, Bartolini L and Inzitari D: Cognitive impairment and chronic cerebral hypoperfusion: What can be learned from experimental models. J Neurol Sci. 203-204:263–266. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Reiter RJ, Tan DX, Osuna C and Gitto E: Actions of melatonin in the reduction of oxidative stress. A review. J Biomed Sci. 7:444–458. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Zhang Y, Li L, Xiang C, Ma Z, Ma T and Zhu S: Protective effect of melatonin against Adriamycin-induced cardiotoxicity. Exp Ther Med. 5:1496–1500. 2013.PubMed/NCBI

16 

Ma J, Shaw VE and Mitrofanis J: Does melatonin help save dopaminergic cells in MPTP-treated mice? Parkinsonism Relat Disord. 15:307–314. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Reiter RJ, Cabrera J, Sainz RM, Mayo JC, Manchester LC and Tan DX: Melatonin as a pharmacological agent against neuronal loss in experimental models of Huntington's disease, Alzheimer's disease and parkinsonism. Ann NY Acad Sci. 890:471–485. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Lee EJ, Lee MY, Chen HY, Hsu YS, Wu TS, Chen ST and Chang GL: Melatonin attenuates gray and white matter damage in a mouse model of transient focal cerebral ischemia. J Pineal Res. 38:42–52. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Letechipía-Vallejo G, López-Loeza E, Espinoza-González V, González-Burgos I, Olvera-Cortés ME, Moralí G and Cervantes M: Long-term morphological and functional evaluation of the neuroprotective effects of post-ischemic treatment with melatonin in rats. J Pineal Res. 42:138–146. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Lee MY, Kuan YH, Chen HY, Chen TY, Chen ST, Huang CC, Yang IP, Hsu YS, Wu TS and Lee EJ: Intravenous administration of melatonin reduces the intracerebral cellular inflammatory response following transient focal cerebral ischemia in rats. J Pineal Res. 42:297–309. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Tyagi E, Agrawal R, Nath C and Shukla R: Effect of melatonin on neuroinflammation and acetylcholinesterase activity induced by LPS in rat brain. Eur J Pharmacol. 640:206–210. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Institute of Laboratory Animal Research, Committee for the Update of the Guide for the Care and Use of Laboratory Animals and National Research Council: Guide for the care and use of laboratory animals (8th). Washington, D.C., USA: National Academies Press. 2202011.

23 

Yoo DY, Kim W, Lee CH, Shin BN, Nam SM, Choi JH, Won MH, Yoon YS and Hwang IK: Melatonin improves D-galactose-induced aging effects on behavior, neurogenesis, and lipid peroxidation in the mouse dentate gyrus via increasing pCREB expression. J Pineal Res. 52:21–28. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Schmued LC and Hopkins KJ: Fluoro-Jade B: A high affinity fluorescent marker for the localization of neuronal degeneration. Brain Res. 874:123–130. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Sugawara T, Lewén A, Noshita N, Gasche Y and Chan PH: Effects of global ischemia duration on neuronal, astroglial, oligodendroglial, and microglial reactions in the vulnerable hippocampal CA1 subregion in rats. J Neurotrauma. 19:85–98. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Qu J, Zhou Q, Du Y, Zhang W, Bai M, Zhang Z, Xi Y, Li Z and Miao J: Rutin protects against cognitive deficits and brain damage in rats with chronic cerebral hypoperfusion. Br J Pharmacol. 171:3702–3715. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Pappas BA, de la Torre JC, Davidson CM, Keyes MT and Fortin T: Chronic reduction of cerebral blood flow in the adult rat: Late-emerging CA1 cell loss and memory dysfunction. Brain Res. 708:50–58. 1996. View Article : Google Scholar : PubMed/NCBI

28 

Li Y, He Y, Guan Q, Liu W, Han H and Nie Z: Disrupted iron metabolism and ensuing oxidative stress may mediate cognitive dysfunction induced by chronic cerebral hypoperfusion. Biol Trace Elem Res. 150:242–248. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Stoll G, Jander S and Schroeter M: Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol. 56:149–171. 1998. View Article : Google Scholar : PubMed/NCBI

30 

Dirnagl U, Iadecola C and Moskowitz MA: Pathobiology of ischaemic stroke: An integrated view. Trends Neurosci. 22:391–397. 1999. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lee CH, Park JH, Ahn JH and Won MH: Effects of melatonin on cognitive impairment and hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion. Exp Ther Med 11: 2240-2246, 2016.
APA
Lee, C.H., Park, J.H., Ahn, J.H., & Won, M. (2016). Effects of melatonin on cognitive impairment and hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion. Experimental and Therapeutic Medicine, 11, 2240-2246. https://doi.org/10.3892/etm.2016.3216
MLA
Lee, C. H., Park, J. H., Ahn, J. H., Won, M."Effects of melatonin on cognitive impairment and hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion". Experimental and Therapeutic Medicine 11.6 (2016): 2240-2246.
Chicago
Lee, C. H., Park, J. H., Ahn, J. H., Won, M."Effects of melatonin on cognitive impairment and hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion". Experimental and Therapeutic Medicine 11, no. 6 (2016): 2240-2246. https://doi.org/10.3892/etm.2016.3216
Copy and paste a formatted citation
x
Spandidos Publications style
Lee CH, Park JH, Ahn JH and Won MH: Effects of melatonin on cognitive impairment and hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion. Exp Ther Med 11: 2240-2246, 2016.
APA
Lee, C.H., Park, J.H., Ahn, J.H., & Won, M. (2016). Effects of melatonin on cognitive impairment and hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion. Experimental and Therapeutic Medicine, 11, 2240-2246. https://doi.org/10.3892/etm.2016.3216
MLA
Lee, C. H., Park, J. H., Ahn, J. H., Won, M."Effects of melatonin on cognitive impairment and hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion". Experimental and Therapeutic Medicine 11.6 (2016): 2240-2246.
Chicago
Lee, C. H., Park, J. H., Ahn, J. H., Won, M."Effects of melatonin on cognitive impairment and hippocampal neuronal damage in a rat model of chronic cerebral hypoperfusion". Experimental and Therapeutic Medicine 11, no. 6 (2016): 2240-2246. https://doi.org/10.3892/etm.2016.3216
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