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Current Clinical Pharmacology, 2019, 14, 1-5 1
RESEARCH ARTICLE
1574-8847/19 $58.00+.00 © 2019 Bentham Science Publishers
Minocycline Increases in-vitro Cortical Neuronal Cell Survival after Laser
Induced Axotomy
Burak Yulug
1,#,*
, Mehmet Ozansoy
2,5,#
, Merve Alokten
2
, Muzaffer Beyza Cetin Ozansoy
2,6
, Seyda
Cankaya
1
, Lutfu Hanoglu
3
, Ulkan Kilic
4
and Ertugrul Kilic
6
1
Alanya Alaaddin Keykubat University, Faculty of Medicine, Department of Neurology, Antalya/Alanya, Turkey;
2
Istanbul Medipol University, Regenerative and Restorative Medicine Research Center, Istanbul, Turkey;
3
Istanbul
Medipol University, Department of Neurology, Faculty of Medicine, Istanbul, Turkey;
4
University of Health Sciences,
Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey;
5
Istanbul Medipol University, International
School of Medicine, Department of Physiology, Istanbul, Turkey;
6
Istanbul Medipol University, School of Medicine,
Department of Physiology, Istanbul, Turkey
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, Ger-
many) 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 stud-
ies that concentrate on the translational block between animal and human studies.
Conclusion: Such sophisticated approaches might also help to conquer the influence of human-
made 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.
1. INTRODUCTION
Axotomy often initiates alterations in the cytology of
nerve cells, changes in specific gene expression, transport of
some neurotrophins and, degeneration of neurons. This proc-
ess is induced retrogradely by depriving these cells of target-
derived trophic support that finally lead to neuronal cell
death. It has been already shown that the evolution of ab-
normalities in neurons depends on several factors. These
include the type of axotomized neurons, location of cell body
lesion, and the intensity of injury [1]. Some studies have
even recognized significant post-lesional differences after
axotomy in specific neuronal cell types indicating that there
*Address correspondence to this author at the Alanya Alaaddin Keykubat
University, Faculty of Medicine, Department of Neurology, Kestel District,
PC:07400, Alanya/Antalya, Turkey; E-mail: byulug@medipol.edu.tr
#
Both authors are equally contributed to this work.
is a variability in implementation of the severity of trauma
that depends on the different type, severity and location of
the lesion [1]. Accordingly, studies have already indicated
that differences in the central nervous system (CNS) injury
(such as dissection and acceleration) might cause a wide
range of clinical complexity [2]. Several types of in-vitro
damage methods in nervous tissue elements have been
shown in controlled culture conditions. In this context, there
have been many tool and techniques (i.e., different mechani-
cal impactors and stretchers) to induce the in-vitro neuronal
injury. However, these techniques did not offer enough stan-
dardization for the applied trauma and failed to mimic direct
mechanical damage on neuronal axons [2]. These findings
together suggested the importance of conducting well-
designed and highly controlled experimental studies to
evaluate the pathophysiological changes of damaged neu-
ronal cells. These novel experimental approaches would also
provide real-time monitoring of the ongoing biomechanical
A R T I C L E H I S T O R Y
Received: December 27, 2018
Revised: January 02, 2019
Accepted: February 16, 2019
DOI:
10.2174/1574884714666190226093119