Neuroinflammation in Sepsis: Molecular Pathways of Microglia Activation
, Camila Zaverucha-do-Valle 2,†, Renaud Fleurance 3,4,5, Tarek Sharshar 4,6, Fernando Augusto Bozza 2,7 and Joana Costa d’Avila 1,8,*Round 1
Reviewer 1 Report
This review presents the molecular pathway of microglia activation in the neuroinflammation associated with sepsis. Microglia is a major player of neuroinflammation in the pathophysiology of sepsis-associated encephalopathy. This review discusses how the brain is affected by peripheral immune activation in sepsis and the role of microglia in these processes. The review provides a helpful contribution to understanding molecular mechanisms of microglia activation in sepsis-associated encephalopathy. There are some minor points that require authors’ attention.
- P2 L64 Please change “SEA" for " SAE ".
- P14 L520 Please change “IL1b" for " IL-1b ".
- P14 L534 Please change “TNFa" for " TNF-a ".
- P15 L569 Please change “Nox-2" for " Nox2 ".
- P15 L571, L572 Please change “NOX-2" for " NOX2 ".
Author Response
We thank reviewer 1 for the comments. We made all the corrections suggested (marked in red in the text), and we checked the whole manuscript for spell and grammar mistakes.
Reviewer 2 Report
My suggestions
- I would explain in a short paragraph (in the introduction) on the association of microglia/inflammation and other neurodegenerative diseases.
- Were any genetic factors identified between inflammatory molecules and SAE?
- A table, which summarizes the inflammatory molecules, involved in sepsis, would be nice.
- For Chapter 10 (Molecular mechanisms of neuronal toxicity in SAE ), I would add an additional figure, which summarizes the toxicity mechanisms
Author Response
We really appreciate the suggestions, they certainly made great improvements to our manuscript.
We answered each question bellow:
- I would explain in a short paragraph (in the introduction) on the association of microglia/inflammation and other neurodegenerative diseases.
We included one paragraph in the introduction explaining the association of microglia/neuroinflammation and other neurodegenerative diseases
- Were any genetic factors identified between inflammatory molecules and SAE?
As far as our knowledge there is not strong association described for susceptibility or resistance to sepsis-associated encephalopathy.
- A table, which summarizes the inflammatory molecules, involved in sepsis, would be nice.
We included a table at the end of the manuscript summarizing the main inflammatory mediators involved in the pathophysiology of SAE and their functions.
- For Chapter 10 (Molecular mechanisms of neuronal toxicity in SAE), I would add an additional figure, which summarizes the toxicity mechanisms
We actually had this figure, but it was misplaced in the manuscript. We modified Figure 3 and we moved it to the end of the manuscript. Figure 3 clearly summarizes the mechanisms of neurotoxicity.
Reviewer 3 Report
The paper reviews the literature on the role of neuroinflammation in sepsis, focusing on the molecular pathways underlying microglial activation.
The paper is well written and easy to read. The different chapters are also well organised and progressively describe how the microglial system is organised, how it functions, what its physiological roles are to eventually explain its involvement in sepsis-related neuroinflammation.
I do not find any major faults.
I finally list a few minor spelling/mistakes for the authors to address.
Figure 1: correct IL6 to IL-6 to uniform with the text
line 131: reduces
line 181: remove "and" and put ", ultimately"
line 199: decreases
line 306: format character
lines 348-349: consider revising the sentence
line 362: replace "leading" to "leads to the"
line 363: produces
line 373: shifts
line 426-427: consider rephrasing
line 432: reference for Cao et al.
line 452: uniform character CX3CR1
lines 459-460: missing ")"
line 460: Zhang reference
line 468: contributes
line 469: recrutiment of
line 471: induces
line 482: doesn't does not
line 483: act
line 508: suggest that
line 509: that may
line 589: sepsis-associated
line 589: manifests
Best regards
Author Response
We thank reviewer 3 for the comments and suggestions. We made all the changes suggested in the text (shown in red), and we also checked the whole manuscript for spell and grammar mistakes. Best regards.
Reviewer 4 Report
The manuscript by Moraes et. al, sum up recent progress in neuroinflammation and sepsis, an emerging research investigation field.
The literature cited is of important relevance and the authors are aiming to introduce their own style, interpretation as well as outlook to this interesting topic. They arrange a review that explore extensively the molecular and cellular basis of the potential sepsis mechanisms involved in the immune response of central nervous system. Moreover, they reported an update about the microglial cells as active players in sepsis-associated encephalopathy (SAE).
This is a well written review and the length of the paper is commensurate with the message.
The review may be accepted for publication in this journal.
Author Response
We thank very much the comments of the reviewer 4.
Round 2
Reviewer 2 Report
Manuscript is acceptable now
Author Response
We thank the reviewer very much for taking the time to review our manuscript so carefully. We made a thorough revision of the text and corrected all the spell and grammar mistakes of the manuscript. Best regards.
