Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells

Round 1

Reviewer 1 Report

In this manuscript, Stoica et al. designed an experimental model mimicking spinal cord injury in chronic ethanol-consuming patients then investigated the cellular and molecular changes with that. A few cell functions have been evaluated such as apoptosis, stress effects and cell recovery ability with the optimized cell model. Overall, the results are supportive and the manuscript was well written. Some comments are listed and suggested below. 

Please have the best resolution for all figures. The quality for figure 5 and 8  is not acceptable. 

Please rephrase line 74.

Please offer enough interpretation in the results. What do those increase or decrease of tested targets mean or suggest, to help readers understand well?

Author Response

Dear reviewer,

Thank you very much for your comments and suggestions. Please see below our response:

Please have the best resolution for all figures. The quality for figure 5 and 8  is not acceptable - we changed the figures and increased the resolution as much as possible

Please rephrase line 74 - the line was rephrased

Please offer enough interpretation in the results. What do those increase or decrease of tested targets mean or suggest, to help readers understand well? - we provide supplementary interpretation in the newly uploaded version of the manuscript. Thank you very much for your suggestion.

Reviewer 2 Report

I have read the manuscript "Molecular aspects of hypoxic stress effects in chronic ethanol 2 exposure of neuronal cells" and would like to share some comments with you. There are several areas in the manuscript that deserve improvements.

 

-          In the manuscript, there was not any citation to a similar induction model for SCI. Is it for the first time using this model or not? Do you have a “reference research” for this SCI in vitro model?

-          For confirming the SCI induction, which experiment was done?

-          In the initiation of result sentences written confusingly, please notice that.

-          Figures 3 and 5 (B) are unclear and need to make with high resolution.  

-          In the discussion section, there is no efficient discussion of previous studies and also similar models of SCI, so need to be a scientific revision.

Author Response

Dear reviewer,

Thank you very much for your suggestions meant for our manuscript improvement. Please see below our responses: 

In the manuscript, there was not any citation to a similar induction model for SCI. Is it for the first time using this model or not? Do you have a “reference research” for this SCI in vitro model?

• Oxygen deprivation is a significant contributor to neurological conditions such as spinal cord injury. The changes produced by vertebral-medullary trauma are initiated by the suffering of neural cells produced by traumatic and vascular (ischemic and hemorrhagic) injuries, followed by local hypoxia (Alizadeh et al., 2019). For these reasons, we used the induction of cell hypoxia in cell cultures as a model of suffering similar to spinal cord trauma.

For confirming the SCI induction, which experiment was done?

• As above mentioned, we generated hypoxia in cell cultures and not SCI in animals. Our aim was only to mimic the detrimental conditions detected in SCI but at the cell cultures level and not at the organ/systemic level. The experimental model is original in terms of explaining the clinical paradox observed through the positive correlation between chronic ethanol consumption and the relatively favorable evolution after SCI, as we showed in a previously published article (Stoica et al., n.d.).

Alizadeh, A., Dyck, S. M., & Karimi-Abdolrezaee, S. (2019). Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms. Frontiers in Neurology, 10, 282. https://doi.org/10.3389/FNEUR.2019.00282

Stoica, S. I., Tănase, I., Ciobanu, V., & Onose, G. (n.d.). Initial researches on neuro-functional status and evolution in chronic ethanol consumers with recent traumatic spinal cord injury. Journal of Medicine and Life, 12, 97–112. https://doi.org/10.25122/jml-2019-0026

In the initiation of result sentences written confusingly, please notice that.

• Thank you, the sentence was rewritten.

Figures 3 and 5 (B) are unclear and need to make with high resolution.

•  the figures were improved in the newly uploaded version of the manuscript.

In the discussion section, there is no efficient discussion of previous studies and also similar models of SCI, so need to be a scientific revision.

• we added new paragraphs to the discussion section regarding previous studies and similar experimental models. Thank you very much for this suggestion.

Round 2

Reviewer 2 Report

All of my comments have been responded satisfactorily.