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Dear Authors,
Our reviewers recommended to accept the manuscript in its current form. However, this is the editorial acceptance and requires a series of tasks to be completed before publication. So, I advise you to be available for few days to complete all the formalities to avoid any delays.
All the best for your future submissions.
Regards
[# PeerJ Staff Note - this decision was reviewed and approved by Gwyn Gould, a PeerJ Section Editor covering this Section #]
all changes are included and the final manuscript is satisfactory.
No recommended changes
No recommended changes
all changes recommended have been included satisfactoriliy
Dear Authors,
Do the needful as suggested by referee and resubmit asap.
All the best
All necessary changes had been included. However it is suggested that the last paragraph (line 114 to 121) may kindly be made second last paragraph and also include the citation of relevant references for the statements given (for example -same as given in discussion- reference 6 to 8). it will improve the logical sequence of the introduction.
the photographs of immunohistochemistry were not found in the revised manuscript. Only immunofluorescence, H&E and Safranin O–fast green were found. Kindly include them as it is an important part of the material and method.
No comments.
no comments
No comments
Dear Authors,
Please address/justify the comments from reviewer/s and resubmit the revision asap.
All the best
The manuscript is well written and describes the findings very clearly.
Introduction
Most humbly it is suggested that in the last paragraph of the introduction a statement about the biomechanical effects of the cervical instability may be included, which indicates how it leads to IVDD.
Figures are relevant, high quality, well labelled & described properly .
Raw data was supplied
The presented research is original primary research within Scope of the journal.
Research question were well defined in the introduction
Material and methods are relevant & meaningful.
It is stated how the research fills an identified knowledge gap.
Rigorous investigation was performed to a high technical & ethical standard.
Comments for Material Methods-
Line 188- “The cervical spine specimens of rats and rats (C2-T2) were collected”- the sentence is not clear, kindly address the issue.
Kindly include a citation/ reference for the method of H&E and safranin staining performed in the study.
Line 210- “60oC water bath for 16 hours for antigen repair, then incubated in hydrogen peroxide solution for….” Kindly explain what is ‘antigen repair’
Line 214-216-
“DAB was stained, hematoxylin was stained, and installed to observe the expression of the corresponding protein using an optical microscope (ZEISS AXIO Imager D2, Germany)” –
In this sentence the expression- ‘DAB was stained, hematoxylin was stained, and installed’, is not scientifically clear. It may kindly be expressed properly to convey a scientifically meaningful indication of the protocol followed.
Line – 222 & 223 All rats and mice that completed the experimental plan were included in the statistical analysis. It is not clear what is meant by ‘completed the experiment’? kindly modify the sentence.
The research will have good impact in concerned field and it is a unique novel work.
No picture of results of immunohistochemistry are shared. Kindly share in the final manuscript.
Following observation regarding discussion are mentioned.
Most humbly it is brought to your kind notice that the discussion started and ended abruptly. There was negligible comparison with earlier published results. The following suggestions may be followed for modifying in the discussion:
• First the topic is introduced by mentioning the hypothesis/reasons for research and objectives in brief with standard but brief chronological review up to recent times.
• Then the findings represented in results are systematically compared with the published research work.
• Then a correlation between the findings is attempted. To show, how they are related to each other or substantiate each other, or even disprove anything.
• Then a meaningful analysis is made to show, how the findings depicted in results complement or contradict the hypothesis.
• Discussion may end with remarks briefly summarizing the salient findings in logical sequence to draw a meaningful conclusion.
Kindly include immunohistochemistry analysis of samples in the photographs. It will improve the impact of analysis.
Dear Authors,
Please go through the comments and suggestions by our referees and do the needful.
All the best.
**PeerJ Staff Note:** Please ensure that all review, editorial, and staff comments are addressed in a response letter and that any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
Clear and professional English is used throughout. The manuscript includes high-quality, properly labeled figures and raw data. Relevant literature and contextual background are adequately cited. Minor editorial improvements are recommended, particularly regarding referencing format (e.g., inconsistent bracket spacing and closure).
This manuscript presents a reproducible animal model for studying cervical intervertebral disc degeneration (IVDD) through bilateral cervical laminectomy and spinous process resection in mice and rats. The authors successfully demonstrate progressive cervical IVDD via MRI, histological, and molecular analyses over a 12-week period. The main takeaway is the establishment of a relatively less invasive, ethically viable, and reproducible model that simulates the chronic degenerative process of human IVDD.
Conclusions
The conclusions are largely supported by the results. The authors demonstrate consistent degeneration across imaging, histology, and molecular markers, with appropriate use of controls and statistical analysis. However, some points need clarification:
- The partial recovery observed at 12 weeks could be better contextualized—does this indicate a regenerative trend or a limitation of the model duration?
- Lack of behavioral or pain-related assessments slightly weakens the translational impact.
- The model does not explore functional consequences such as neural involvement or mobility impairment, which would enhance clinical relevance.
Significance of the Conclusions
The conclusions are important. The study introduces a novel model that better mimics the chronic progression of cervical IVDD, which may have significant utility in preclinical testing of therapeutic strategies and in mechanistic research. It fills a crucial gap in existing animal models that are either too aggressive or not representative of chronic human pathology.
The research question is clear, well-defined, and within scope. Ethical approval is explicitly stated, and procedures are designed to minimize stress and avoid direct disc injury. The methodology is replicable and ethically sound. However, the rationale for sample size is not discussed, and no a priori power analysis is provided. Additionally, the absence of behavioral (pain-related) outcome measures limits the relevance of findings in the context of spine degeneration studies.
Findings are well-supported by statistically analyzed imaging, histology, and molecular data, which show strong alignment and consistency with the stated hypothesis. MRI and histological results correlate effectively with molecular markers. However, the study lacks long-term follow-up beyond 12 weeks and omits functional or neurological outcome measures (e.g., motor deficits, pain behaviors).
This is an important contribution to the field of spine research. The model is well designed and thoughtfully executed, offering a more physiologically relevant approach than previously available models. To improve the translational utility, consider including behavioral assessments in future work to correlate structural degeneration with functional impairment. Clarify rationale for the 12-week endpoint—do authors plan to assess longer-term outcomes?
Discuss clinical implications—how might this model help test biologics or regenerative interventions?
- Functional/pain assessments
- Longer follow-up for chronicity
- Slight improvements in formatting
The manuscript presents animal studies aimed at developing models of cervical intervertebral disc degeneration that mimic the process of human intervertebral disc degeneration.
A key concern regarding the results is the observed trend towards improvement in MRI and histological findings of intervertebral disc degeneration at the 12-week time point. This trend significantly diverges from the typical presentation of human disc degeneration.
While this animal model induces disc degeneration through extensive laminectomy in the cervical spine, the study did not assess whether cervical instability or alterations in cervical alignment occurred. It is necessary to evaluate radiographs or CT data to evaluate these potential factors.
Line 161: Detailed MRI scanning parameters, including information about the MRI equipment, should be provided.
Lines 234 to 241: The reviewer cannot identify the progressive disc degeneration in Figures A and C. The authors should reference the manuscript describing Pfirrmann’s classification. In the original Pfirrmann’s classification, grade I indicates a normal disc, while grade V indicates a severely degenerated disc.
Figure 1: All figures should be numbered. What are the differences between the two images in Figure A and Figure B? In the figure legends, the term "cervical disc exposure" is mentioned, but the reviewer cannot identify this exposure in Figures A and B.
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