Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy
- Wenzhou Medical University, China
- Beijing Institute of Technology, China
- Stanford University, United States
- Second Affiliated Hospital, Wenzhou Medical University, China
- Third Affiliated Hospital of Sun Yat-sen University, China
- National Eye Institute (NIH), United States
Abstract
Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: 1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. 2) Even with possible access for “local refrigeration”, cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4°C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas.
Data availability
Computer program download site:https://github.com/LujieZhang/Preoperative-planning.The processed gene expression data in this paper have been deposited into the NCBI GEO database: GSE182164. RNA-seq data download site: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?&acc=GSE182164.
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Author details
Funding
National Key Research and Development Program of China Stem Cell and Translational Research (2021YFA1101200)
- Wencan Wu
National Key Research and Development Program of China (2016YFC1101200)
- Wencan Wu
National Natural Science Foundation of China (81770926)
- Wencan Wu
National Natural Science Foundation of China (81800842)
- Yikui Zhang
Key R&D Program of Zhejiang Province (2018C03G2090634)
- Wencan Wu
Key R&D Program of Zhejiang Province (2021C03065)
- Wencan Wu
Key R&D Program of Wenzhou Eye Hospital (YNZD1201902)
- Wencan Wu
National Key Research and Development Program of China (2019YFC0119300)
- Jian Yang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments were conducted following the Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use of Animals in Ophthalmic and Vision Research guidelines.All protocols were approved by the Institutional Animal Care and Use Committee in the Wenzhou Medical University (Wenzhou, China, ID number: wydw2020-0789) and the Joinn Laboratory (Suzhou, China, ID number: P19-S445-PD).
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy
eLife 11:e75070.
https://doi.org/10.7554/eLife.75070
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Background: Several fields have described low reproducibility of scientific research and poor accessibility in research reporting practices. Although previous reports have investigated accessible reporting practices that lead to reproducible research in other fields, to date, no study has explored the extent of accessible and reproducible research practices in cardiovascular science literature.
Methods: To study accessibility and reproducibility in cardiovascular research reporting, we screened 639 randomly selected articles published in 2019 in three top cardiovascular science publications: Circulation, the European Heart Journal, and the Journal of the American College of Cardiology (JACC). Of those 639 articles, 393 were empirical research articles. We screened each paper for accessible and reproducible research practices using a set of accessibility criteria including protocol, materials, data, and analysis script availability, as well as accessibility of the publication itself. We also quantified the consistency of open research practices within and across cardiovascular study types and journal formats.
Results: We identified that fewer than 2% of cardiovascular research publications provide sufficient resources (materials, methods, data, and analysis scripts) to fully reproduce their studies. Of the 639 articles screened, 393 were empirical research studies for which reproducibility could be assessed using our protocol, as opposed to commentaries or reviews. After calculating an accessibility score as a measure of the extent to which an article makes its resources available, we also showed that the level of accessibility varies across study types with a score of 0.08 for Case Studies or Case Series and 0.39 for Clinical Trials (p = 5.500E-5) and across journals (0.19 through 0.34, p = 1.230E-2). We further showed that there are significant differences in which study types share which resources.
Conclusion: Although the degree to which reproducible reporting practices are present in publications varies significantly across journals and study types, current cardiovascular science reports frequently do not provide sufficient materials, protocols, data, or analysis information to reproduce a study. In the future, having higher standards of accessibility mandated by either journals or funding bodies will help increase the reproducibility of cardiovascular research.
Funding: Authors Gabriel Heckerman, Arely Campos-Melendez, and Chisomaga Ekwueme were supported by an NIH R25 grant from the National Heart, Lung and Blood Institute (R25HL147666). Eileen Tzng was supported by an AHA Institutional Training Award fellowship (18UFEL33960207).
