Impaired Peripheral Vascular Function Following Ischemic Stroke in Mice: Potential Insights into Blood Pressure Variations in the Post-Stroke Patient

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This study by Drs. Yimaz and Alexander addresses the clinically significant issue of Impaired Peripheral Vascular Function Following Ischemic Stroke and its implications for blood pressure variations in post-stroke patients. The study aims to elucidate changes in vasomotor function in isolated peripheral arteries following ischemic stroke. Using wire myography, the researchers quantified the reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors. They found that endothelium-dependent vasodilation induced by acetylcholine was impaired after ischemic stroke. Interestingly, vasodilatory responses to SNP were similar in isolated aortas from both sham and stroke groups. However, phenylephrine-induced vasoconstriction was diminished in aortas isolated from stroke animals compared to sham counterparts.

Although this study is informative, it is somewhat limited in scope. It provides insights into the increased variability of blood pressure following ischemic stroke. One suggestion for improvement is to simplify the summary figure, as it currently appears complex and may be challenging to interpret. Additionally, the discussion section could be more concise.

Overall, this research contributes valuable findings to our understanding of vascular dysfunction post-ischemic stroke, highlighting potential implications for clinical management.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

Reviewer report: 05.07.2024

“Impaired Peripheral Vascular Function Following Ischemic Stroke: Implications for blood pressure variations in the post-stroke patient.”

 

In the original research article “Impaired Peripheral Vascular Function Following Ischemic Stroke: Implications for blood pressure variations in the post-stroke patient” the authors have aimed at assessing the vasomotor function in isolated peripheral arteries following ischemic stroke by measuring both vasoconstriction and endothelium-dependent as well as endothelium-independent vasodilation responses in murine aortas post-stroke. Interestingly, the authors could show intact endothelium-independent vasodilatory responses, as well as impaired vasodilatory and vasoconstrictor responses after ischemic stroke.

 

This article’s strength is that it addresses an important topic – blood pressure variation post-stroke aiming to uncover underlying mechanisms.

 

Major comments:

The title of your research article is misleading, as it states that the results have implications for blood pressure variations in the post-stroke patient. However, the title should communicate succinctly the findings of the completed research which has only dealt with C57BL/6 mice. 

 

Unfortunately, studies haven’t demonstrated a causal relationship between blood pressure variability and stroke outcome in patients so far. In addition, blood pressure variability in stroke patients might also be influenced by the autonomic nervous function, cardiopulmonary reflex, inflammation, body temperature, pain etc. These factors should be added in this manuscript. The rush from bench to bedside should be reevaluated.

 

Introduction:

·      I am not content with the statement that “current therapies are limited to maintenance of normal homeostasis and prevention and prompt treatment of secondary insults”. Endovascular therapy and thrombolysis do exceed “maintenance of normal homeostasis” (Campbell BC et al. N Engl J Med. 2015;372(11):1009-1018.)

 

Concerning the Materials & Methods section:

·      Please include an approval/reference number concerning the statement from the Animal Care and Use Committee and specify the date this was granted, e.g., “… Institute (xx-xx-xx, date of approval: DD-MM-YYYY).

·       How old were the mice included in this experiment? Would you expect a different result with older mice?

·       Please explain why you didn’t use Doppler flow for monitoring the cerebral blood flow while performing MCAO.

 

 

Other comments:

·      Please add references in the introduction for ll. 33-35 (Virani et al. Circulation. 2021;143(8):e254-e743)

·      Materials and methods: In line 91 you state that the sham group was exposed to 1h of MCAO, please correct.

·      For infarct volumetry I would recommend Friedländer et al. J Cereb Blood Flow Metab. 2017;37(8):3015-3026 (Figure 7).

·      Please comment on the decision for the implementation of acetylcholine, sodium nitroprusside and phenylephrine.

·      Please explain why the blood pressure of the mice was not measured beforehand.

·      Inflammation is critical for the development and maintenance of hypertension. Please elaborate on the role of neutrophils in hypertension.

·      Please add the following reference in line 287: Lucaciu et al. Int J Mol Sci. 2020;21(17):6242, Iadecola et al. J Clin Invest. 2020 Jun 1;130(6):2777-2788, enhancing the immune responses to stroke.

 

 

Typographical/grammar (suggested corrections in bold):

 

·      3.1.4 Infarct Size: “In sham group no infarct was observed.”

·      Line 222, a full stop at the end of the sentence is missing.

 

 

I would strongly encourage the authors to take my well-meant suggestions to heart, as I am convinced, they would immensely improve the impact of your article. I am looking forward to reviewing the revised version of this manuscript.

 

Yours sincerely,

Reviewer.

 

Comments on the Quality of English Language

Minor edits required.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Dear all,

Thank you for revising your manuscript. Overall recommendation: Accept.

Kind regards,

Reviewer.

Comments on the Quality of English Language

Minor editing has been performed.

Author Response

Dear Reviewer,

Thank you very much for your valuable time and excellent contributions to our manuscript.

Sincerely yours,

Gokhan