Characterizing the Impact of Compression Duration and Deformation-Related Loss of Closure Force on Clip-Induced Spinal Cord Injury in Rats

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have attempted to characterize the impact of compression duration and mechanical fatigue on clip-induced spinal cord injury in rats. In the studies on the effects of experimental mechanical spinal cord injuries, the compression duration is the most important factor but the range of the structural deficits is usually evaluated in histological, cross-sectional, or sagittal images.

The proposed by authors term "mechanical fatigue" of the compressed spinal cord is an interesting topic, not been studied in detail before, which might influence the expected rate and extent of functional recovery in both basic and clinical studies in animals and patients with incomplete spinal cord injury. In the presented study rats received T10-level clip-induced SCI  with the same force and duration of 1, 5, 10, 20, and 30 seconds, and a separate group underwent T10 transection. The outcomes included functional, histological, electrophysiological assessments (SSEPs), and inflammatory cytokine analysis.  A tactile pressure mapping system quantified clip closure force after open-close cycles. In my opinion, they should not use the term "mechanical fatigue" (the spinal cord structures and surrounding durae do not undergo the fatigue which is a physical and physiological variable) but the phenomenon they have found after five open-close clip cycles can be defined as more "irreversible structural injury". This has been expressed in functional SSEPs recordings and has already been reported in the Abstract, although the histological and functional results have been silenced as well as the biochemical results. Authors only mentioned “deficits comparable to moderate-to-severe SCI-spinal cord injury”.

Taking into account the necessary improvements in the paper, as above, first the change of the title is suggested and the presentation in the Abstract with all the study’s outcomes should be considered. 

The keywords “mechanical endurance;  mechanical fatigue;” should be considered as necessary to be improved. These are the physical variables that do not describe the spinal cord injury properties.

In the Material and Methods section the principles of SSEPs stimulation and recordings should be more precisely described (what was stimulated, which nerve structures, ortho- or antidromic stimulation of the sensory fibers was considered and how was it interpreted in SSEPs recordings?).

 

No interpretation and discussion of the histological and electrophysiological data was provided in the Discussion section.

Comments on the Quality of English Language

Major revisions

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

The paper presented for review reports the results of aneurysm clip compression of the low thoracic spinal cord levels in rats. Motor deficit, SSEP abnormality, morphological changes and the expression of cytokines were studied after compression durations from 1 to 30 sec at a closure force of 80 g that is the standard for Sugita type clip. Additionally, the authors studied changes in the closure force after manipulation of the clip – repetitive opening/closure for different number of times.

Compression models of spinal cord injury are usually applied when the outcome of interest is related to the effects of continuous narrowing of the spinal canal, resp to the timing of decompression. Aneurysm clips are widely used, as they provide a standardized closure force; reports of such studies numbered over 200 about 5 years ago (Sharif-Alhoseini et al, Spinal Cord 2017). In this sense, the research offered is not new as a concept. The results are not unexpected either, as even clamping with 20 g closure force causes cavitation lesions in rat SCI model (Poon et al, Spine 2007), 50 g in the rat lead to complete SCI equal to ASIA A (Weaver et al J Neurotrauma 2001) and the authors applied 80 g although over a very short period. However, this study has the advantage of high technical standards and of assessing the outcomes along four axes (behavioral, structural, electrophysiological and cytokine markers); the research adds to the positive knowledge on SCI after certain patterns of experimental injury, so the publication is expected to attract the audience interested in neurotrauma and spinal cord pathology. The finding of increased expression of the neuroprotective TIMP-1 is interesting, but not much discussed upon. The change in SSEP 4 weeks after the lesion, that parallels in severity the duration of compression could be commented wider as well, possibly looking for some correlation between histological degree of injury and SSEP abnormality. 

The authors also measured the change in closure force of the aneurysmal clips and detected a decrease in closure force even after only 5-10 times opening the clip. One doesn’t expect the clip for such study to be used multiple times, but this finding of clip fatigue, which has been of interest to neurosurgeons as well (Horiuchi 2013), might be methodologically important as the response to compression depends on the closure force, so the experimenter should avoid excessive manipulation of the clip.

In summary, the paper is technically sound, contributing to scientific knowledge and well written and illustrated; I believe it should be accepted for publication. However, I would expect the following improvements. 1) Formulate the hypothesis. What did the authors want to prove or disprove, using the chosen paradigm of very intensive, but very brief compression; 2) comment on possible reasons for the absence of proinflammatory response in this paradigm, 3) some expounding on the causes of permanent changes in SSEP, with parallel to some previous studies.

Author Response

Please see the attachment 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have addressed my suggestions well, although I would rather see a correction of the title to: „Characterizing the Impact of Compression Duration and Deformation-related Loss of Closure Force on Clip-Induced Spinal Cord Injury in Rats” since it is not confusing.

I leave the final decision to the Editor on this issue.

 

The article in the corrected, current form can printed in the journal. 

Comments on the Quality of English Language

The authors have addressed my suggestions well, although I would rather see a correction of the title to: „Characterizing the Impact of Compression Duration and Deformation-related Loss of Closure Force on Clip-Induced Spinal Cord Injury in Rats” since it is not confusing.

I leave the final decision to the Editor on this issue.

 

The article in the corrected, current form can printed in the journal.