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Advanced Pharmaceutical Bulletin
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Article History
Submitted: 08 Jan 2015
Revised: 28 Jun 2015
Accepted: 30 Jul 2015
First published online: 30 Nov 2015

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Adv Pharm Bull. 2015;5(4):515-521 doi: 10.15171/apb.2015.070
PMID:26819924        PMCID:PMC4729347

Paracrine Neuroprotective Effects of Neural Stem Cells on Glutamate-Induced Cortical Neuronal Cell Excitotoxicity

Original Research

Mohammad Hossein Geranmayeh 1, Ali Baghbanzadeh 1 * , Abbas Barin 2, Jamileh Salar-Amoli 3, Mohammad Mehdi Dehghan 4, Reza Rahbarghazi 5, Hassan Azari 6,7

1 Section of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
2 Department of Microbiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
3 Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
4 Department of Surgery and Radiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
5 Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
6 Neural Stem Cell and Regenerative Neuroscience Laboratory, Department of Anatomical Sciences, Shiraz School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
7 Neural Stem Cell and Regenerative Neuroscience Laboratory, Shiraz Stem Cell Institute, Shiraz University of Medical Sciences, Shiraz, Iran.



Abstract
Purpose: Glutamate is a major excitatory neurotransmitter in mammalian central nervous system. Excessive glutamate releasing overactivates its receptors and changes calcium homeostasis that in turn leads to a cascade of intracellular events causing neuronal degeneration. In current study, we used neural stem cells conditioned medium (NSCs-CM) to investigate its neuroprotective effects on glutamate-treated primary cortical neurons. Methods: Embryonic rat primary cortical cultures were exposed to different concentrations of glutamate for 1 hour and then they incubated with NSCs-CM. Subsequently, the amount of cell survival in different glutamate excitotoxic groups were measured after 24 h of incubation by trypan blue exclusion assay and MTT assay. Hoechst and propidium iodide were used for determining apoptotic and necrotic cell death pathways proportion and then the effect of NSCs-CM was investigated on this proportion. Results: NSCs conditioned medium increased viability rate of the primary cortical neurons after glutamate-induced excitotoxicity. Also we found that NSCs-CM provides its neuroprotective effects mainly by decreasing apoptotic cell death rate rather than necrotic cell death rate. Conclusion: The current study shows that adult neural stem cells could exert paracrine neuroprotective effects on cortical neurons following a glutamate neurotoxic insult.





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