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The authors have addressed all of the reviewers' comments and the manuscript is ready for publication.
The related issues have been modified, and it is recommended to accept.
None.
None.
O manuscrito está bem escrito. Contém referências suficientes para a compreensão dos resultados. Os resultados estão devidamente apresentados e os dados brutos foram anexados.
O desenho experimental é adequado. As alterações no texto realizadas pelos autores melhoraram a compreensão dos métodos utilizados para obtenção dos dados.
The data are valid and contribute to the understanding of the pathophysiological processes related to neuroinflammation observed in perioperative neurocognitive disorders.
The authors made changes to the text to clarify doubts raised in the first review.
Dear Dr. Yao,
We have received two reviews of your manuscript. As you can see from the reviewers' comments, the current manuscript requires revision before it can be considered for publication in PeerJ. We strongly recommend that you carefully consider the reviewers' suggestions, especially regarding the experimental design and rationale, data interpretation, and additional clarifications requested.
Please submit a revised version of your manuscript that addresses these points, incorporating the proposed changes and improvements.
In the manuscript ‘Surgery-induced neuroinflammatory transcriptional programs in medial prefrontal cortex of mice during early phase of perioperative neurocognitive disorders’, the authors explored the neuroinflammatory mechanisms of medial prefrontal cortex in the development of perioperative neurocognitive disorders, and provided a new foundation for understanding PND pathophysiology. However, it has several aspects which need further revisions.
Major Comments:
1.Cognitive function is typically considered to be closely associated with hippocampus. Why did this study not involve both hippocampus and prefrontal cortex?
2. Open-field test is commonly used to assess emotions and habituation. Why was it used in this experiment evaluating cognition?
3. Please explain why the surgical method “aseptic open tibial fracture surgery with intramedullary" was chosen. Would this choice impact the sensory and actions of the mice in the behavioral tests?
4. Please provide the reason for this phenomenon “Interleukin-6 level increased in both serum and mPFC, while the mRNA levels of Il-6, Tnf-α, and Il-1β remained unchanged.”
5. Previous studies (Gonçalves J, Martins T et al. PMID: 18991854) have shown that both IL-6 and IL-6 mRNA levels increase during inflammation. Why did that result contradict the present result.
6. The current GO and KEGG results are relatively scattered. Please further analyze the GO and KEGG results to distill the inflammation-related pathways and mechanisms.
7. Please provide selection criteria for the 15 DEGs in qRT-PCR analysis?
Minor Comments:
1. Please annotate main DEGs in Figure 2B.
2. Please assign subtitles to the subfigures in Figure 3.
1.Cognitive function is typically considered to be closely associated with hippocampus. Why did this study not involve both hippocampus and prefrontal cortex?
2. Open-field test is commonly used to assess emotions and habituation. Why was it used in this experiment evaluating cognition?
3. Please explain why the surgical method “aseptic open tibial fracture surgery with intramedullary" was chosen. Would this choice impact the sensory and actions of the mice in the behavioral tests?
4. Please provide the reason for this phenomenon “Interleukin-6 level increased in both serum and mPFC, while the mRNA levels of Il-6, Tnf-α, and Il-1β remained unchanged.”
5. Previous studies (Gonçalves J, Martins T et al. PMID: 18991854) have shown that both IL-6 and IL-6 mRNA levels increase during inflammation. Why did that result contradict the present result.
In the manuscript entitled “Surgery-induced neuroinflammatory transcriptional programs in medial prefrontal cortex of mice during early phase of perioperative neurocognitive disorders”, Tang and colleagues have found that 6 h post-surgery (tibial fracture under general anesthesia - 3.0% isoflurane followed by maintenance with 2.0% isoflurane in 30% FiO2), in the medial pre-frontal cortex (mPFC) of mice, 105 genes were upregulated and 73 genes were downregulated. In addition, interleukin-6 level increased in both serum and mPFC, while the mRNA levels of Il-6, Tnf-³, and Il-1³ remained unchanged. The authors suggest the findings represent a “distinct and acute neuroinflammatory response in the mPFC is evoked after peripheral surgery”. Such neuroinflammatory response might be related to the development of perioperative neurocognitive disorders (PND), a well-characterized phenomenon in the literature.
The manuscript is well written, concise, well structured, well referenced, and clear. The figures are clear and relevant. The raw data was supplied.
The methods described seem to be well conducted. However, in the MIQE checklist not all the essential information were provided. It is not clear how the mPFC were identified and collected from the fresh brain.
The findings are relevant to the field. Conclusions are linked to the objective or the study. However, in my opinion, the authors should comment about the possibility of inflammation occurring in other brain areas or include results of the analysis of brain tissue surrounding the mPFC, as demonstration of selectivity.
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