Neuroinflammation and Precision Medicine in Pediatric Neurocritical Care: Multi-Modal Monitoring of Immunometabolic Dysfunction

Round 1

Reviewer 1 Report

This is a nice and well done review on neuroinflammation of pediatric critical care. The Authors should describe the role of oxidative stress in the neuroinflammation of this clinical setting. Endothelial damage should be more discussed and the markers of endothelial damage should be identified. Moreover the role of cytokines in the neuroinflammation of pediatric critical care has to be better analyzed.

The Introduction Is accurate and explains in details the aim of the study. The content Is complete, but the Author's should discuss the role of oxidative stress on neuroinflammation of critical pediatric care. More specific details should be described about the endotelial damage in this clinical setting. The scientific soundness Is relevant, but the cytokines specific role in neuroinflammation has to be discussed. The presentation qualiity Is very good and the different chapters are good differentiated. The interest to the readers Is very large and this review represent a very interesting point of view in this clinical setting. Finally this review Is very nice and need only of a minor revision to be published.

Author Response

Response to reviewers:

 

We thank the reviewers for taking the time to thoroughly review the article, and provide significant input into areas of improvement for the article.

 

Reviewer 1:

 

This is a nice and well done review on neuroinflammation of pediatric critical care. The Authors should describe the role of oxidative stress in the neuroinflammation of this clinical setting. Endothelial damage should be more discussed and the markers of endothelial damage should be identified. Moreover the role of cytokines in the neuroinflammation of pediatric

critical care has to be better analyzed. The Introduction Is accurate and explains in details the aim of the study. The content Is complete, but the Author's should discuss the role of oxidative stress on neuroinflammation of critical pediatric care. More specific neuroinflammation has to be discussed. The presentation quality Is very good and the different chapters are good differentiated. The interest to the readers Is very large and this review represent a very interesting point of view in this clinical setting. Finally this review Is very nice and need only of a minor revision to be published.

 

Response: We thank the review for providing areas of improvement within the article. The suggestions additions will serve to improve the manuscript. We have further elaborated on the role of oxidate stress and endothelial damage within paragraph 6 of the introduction, under the heading ‘CNS neuroinflammation and immunometabolism’. These changes have been highlighted within track changes. In addition, we have added a paragraph about the role of cytokines in neuroinflammation, and this can be viewed in paragraph 7 of the introduction under the heading ‘CNS neuroinflammation and immunometabolism’, which is also highlighted using track changes.

Reviewer 2 Report

The review by Woodward et al., provides an important summary on Neuroinflammation.

Neuroinflammation is considered at the center of CNS neurodegenerative diseases.  The article has both basic mechanisms and clinical approaches for the understanding and treatment of  neuroinflammation. Thus the value of this review extends to other diseases of the CNS. 

The writing is direct and easy to follow.  Similarly,  the figures are instructive of complex events.

Author Response

We thank the reviewers for taking the time to thoroughly review the article, and provide significant input into areas of improvement for the article.

Reviewer 2:

The review by Woodward et al., provides an important summary on Neuroinflammation. Neuroinflammation is considered at the center of CNS neurodegenerative diseases. The article has both basic mechanisms and clinical approaches for the understanding and treatment of neuroinflammation. Thus the value of this review extends to other diseases of the CNS. The writing is direct and easy to follow. Similarly, the figures are instructive of complex events.

Response: We thank the reviewer for their comments towards the review article.

Round 2

Reviewer 1 Report

The role of oxidative stress in neuroinflammatory critical care is now well described. Also the behaviour of cytokines in thi clinical setting is now largely examinated