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Current Clinical Pharmacology

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ISSN (Print): 1574-8847
ISSN (Online): 2212-3938

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Research Article

Minocycline Increases in-vitro Cortical Neuronal Cell Survival after Laser Induced Axotomy

Author(s): Burak Yulug*, Mehmet Ozansoy, Merve Alokten, Muzaffer B.C. Ozansoy, Seyda Cankaya, Lutfu Hanoglu, Ulkan Kilic and Ertugrul Kilic

Volume 15, Issue 2, 2020

Page: [105 - 109] Pages: 5

DOI: 10.2174/1574884714666190226093119

Abstract

Background: Antibiotic therapies targeting multiple regenerative mechanisms have the potential for neuroprotective effects, but the diversity of experimental strategies and analyses of non-standardised therapeutic trials are challenging. In this respect, there are no cases of successful clinical application of such candidate molecules when it comes to human patients.

Methods: After 24 hours of culturing, three different minocycline (Sigma-Aldrich, M9511, Germany) concentrations (1 μM, 10 μM and 100 μM) were added to the primary cortical neurons 15 minutes before laser axotomy procedure in order to observe protective effect of minocycline in these dosages.

Results: Here, we have shown that minocycline exerted a significant neuroprotective effect at 1 and 100μM doses. Beyond confirming the neuroprotective effect of minocycline in a more standardised and advanced in-vitro trauma model, our findings could have important implications for future studies that concentrate on the translational block between animal and human studies.

Conclusion: Such sophisticated approaches might also help to conquer the influence of humanmade variabilities in critical experimental injury models. To the best of our knowledge, this is the first study showing that minocycline increases in-vitro neuronal cell survival after laser-axotomy.

Keywords: Minocycline, laser-axotomy, in-vitro cortical cell culture, translational neuroscience, trauma, propidium.

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[1]
Koliatsos VE, Price DL. Axotomy as an experimental model of neuronal injury and cell death. Brain Pathol 1996; 6(4): 447-65.
[http://dx.doi.org/10.1111/j.1750-3639.1996.tb00875.x] [PMID: 8944316]
[2]
Cengiz N, Oztürk G, Erdoğan E, Him A, Oğuz EK. Consequences of neurite transection in vitro. J Neurotrauma 2012; 29(15): 2465-74.
[http://dx.doi.org/10.1089/neu.2009.0947] [PMID: 20121423]
[3]
Ma YH, Zeng X, Zhang K, Zeng YS. A new in vitro injury model of mouse neurons induced by mechanical scratching. Neurosci Lett 2012; 510(1): 14-9.
[http://dx.doi.org/10.1016/j.neulet.2011.12.061] [PMID: 22245654]
[4]
Wu T, Mohanty S, Gomez-Godinez V, et al. Neuronal growth cones respond to laser-induced axonal damage. J R Soc Interface 2012; 9(68): 535-47.
[http://dx.doi.org/10.1098/rsif.2011.0351] [PMID: 21831892]
[5]
Levkovitch-Verbin H, Waserzoog Y, Vander S, Makarovsky D, Ilia P. Minocycline mechanism of neuroprotection involves the Bcl-2 gene family in optic nerve transection. Int J Neurosci 2014; 124(10): 755-61.
[http://dx.doi.org/10.3109/00207454.2013.878340] [PMID: 24410139]
[6]
Czeiter E, Pal J, Kovesdi E, et al. Traumatic axonal injury in the spinal cord evoked by traumatic brain injury. J Neurotrauma 2008; 25(3): 205-13.
[http://dx.doi.org/10.1089/neu.2007.0331] [PMID: 18352834]
[7]
Howell GR, Libby RT, Jakobs TC, et al. Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. J Cell Biol 2007; 179(7): 1523-37.
[http://dx.doi.org/10.1083/jcb.200706181] [PMID: 18158332]
[8]
Kelestemur T, Yulug B, Caglayan AB, et al. Targeting different pathophysiological events after traumatic brain injury in mice: Role of melatonin and memantine. Neurosci Lett 2016; 612: 92-7.
[http://dx.doi.org/10.1016/j.neulet.2015.11.043] [PMID: 26639427]
[9]
Yulug B, Kilic E, Altunay S, et al. Cinnamon polyphenol extract exerts neuroprotective activity in traumatic brain injury through modulation of Nfr2 and cytokine expression. CNS Neurol Disord Drug Targets 2018; 17(6): 439-47.
[http://dx.doi.org/10.2174/1871527317666180501110918]
[10]
Sanchez Mejia RO, Ona VO, Li M, Friedlander RM. Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery 2001; 48(6): 1393-9.
[http://dx.doi.org/10.1227/00006123-200106000-00051] [PMID: 11383749]
[11]
Lee JH, Tigchelaar S, Liu J, et al. Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury. Exp Neurol 2010; 225(1): 219-30.
[http://dx.doi.org/10.1016/j.expneurol.2010.06.018] [PMID: 20599974]
[12]
Hanlon LA, Raghupathi R, Huh JW. Differential effects of minocycline on microglial activation and neurodegeneration following closed head injury in the neonate rat. Exp Neurol 2017; 290: 1-14.
[http://dx.doi.org/10.1016/j.expneurol.2016.12.010] [PMID: 28038986]
[13]
Gordon PH, Moore DH, Miller RG, et al. Efficacy of minocycline in patients with amyotrophic lateral sclerosis: A phase III randomised trial. Lancet Neurol 2007; 6(12): 1045-53.
[http://dx.doi.org/10.1016/S1474-4422(07)70270-3] [PMID: 17980667]
[14]
Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain 2012; 135(Pt 4): 1224-36.
[http://dx.doi.org/10.1093/brain/aws072] [PMID: 22505632]
[15]
Casha S, Rice T, Stirling DP, et al. Cerebrospinal fluid biomarkers in human spinal cord injury from a phase II minocycline trial. J Neurotrauma 2018; 35(16): 1918-28.
[http://dx.doi.org/10.1089/neu.2018.5899] [PMID: 30074872]
[16]
Scott G, Zetterberg H, Jolly A, et al. Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration. Brain 2018; 141(2): 459-71.
[http://dx.doi.org/10.1093/brain/awx339] [PMID: 29272357]

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