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3. Collagen Turnover in Relation to Risk Factors and Hemodynamics in Human Intracranial Aneurysms

Author

Hackenberg, Katharina AM, Rajabzadeh-Oghaz, Hamidreza, Dreier, Rita, Buchholz, Bruce A, Navid, Ali, Rocke, David M, Abdulazim, Amr, Hänggi, Daniel, Siddiqui, Adnan, Macdonald, R Loch, Meng, Hui, and Etminan, Nima

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Prevention, Brain Disorders, Adult, Aged, Aneurysm, Ruptured, Collagen, Collagen Type I, Female, Hemodynamics, Humans, Hypertension, Intracranial Aneurysm, Logistic Models, Male, Middle Aged, Models, Theoretical, ROC Curve, Radiometric Dating, Risk Assessment, Risk Factors, Smoking, Vascular Remodeling, collagen, humans, intracranial aneurysm, logistic models, risk factors, Cardiorespiratory Medicine and Haematology, Neurology & Neurosurgery, Clinical sciences, Allied health and rehabilitation science
Abstract

Background and Purpose- Determinants for molecular and structural instability, that is, impending growth or rupture, of intracranial aneurysms (IAs) remain uncertain. To elucidate this, we endeavored to estimate the actual turnover rates of the main molecular constituent in human IA (collagen) on the basis of radiocarbon (14C) birth dating in relation to IA hemodynamics. Methods- Collagen turnover rates in excised human IA samples were calculated using mathematical modeling of 14C birth dating data of collagen in relation to risk factors and histological markers for collagen maturity/turnover in selected IA. Hemodynamics were simulated using image-based computational fluid dynamics. Correlation, logistic regression, and receiver operating characteristic analyses were performed. Results- Collagen turnover rates were estimated in 46 IA (43 patients); computational fluid dynamics could be performed in 20 IA (20 patients). The mean collagen turnover rate (γ) constituted 126% (±1% error) per year. For patients with arterial hypertension, γ was greater than 2600% annually, whereas γ was distinctly lower with 32% (±1% error) per year for patients without risk factors, such as smoking and hypertension. There was a distinct association between histological presence of rather immature collagen in human IA and the presence of modifiable risk factors. Spatial-temporal averaged wall shear stress predicted rapid collagen turnover (odds ratio, 1.6 [95% CI, 1.0-2.7]). Receiver operating characteristic analysis demonstrated a good test accuracy (area under the curve, 0.798 [95% CI, 0.598-0.998]) for average wall shear stress with a threshold ≥4.9 Pa for rapid collagen turnover. Conclusions- Our data indicate that turnover rates and stability of collagen in human IA are strongly associated with the presence of modifiable risk factors and aneurysmal hemodynamics. These findings underline the importance of strict risk factor modification in patients with unruptured IA. Future should include more detailed risk factor data to establish a more causal understanding of hemodynamics and the rupture risk of individual IA.

Published
2020

5. Editor's Choice – Peri-Operative Outcomes of Carotid Endarterectomy are Not Improved on Dual Antiplatelet Therapy vs. Aspirin Monotherapy: A Systematic Review and Meta-Analysis

Author

Ku, Jerry C., Taslimi, Shervin, Zuccato, Jeffrey, Pasarikovski, Christopher R., Nasr, Nathalie, Chechik, Ofir, Chisci, Emiliano, Bissacco, Daniele, Larrue, Vincent, Rabinovich, Yefim, Michelagnoli, Stefano, Settembrini, Piergiorgio G., Priola, Stefano M., Cusimano, Michael D., Yang, Victor X.D., and Macdonald, R. Loch

Published
2022
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15. CFTR Therapeutics Normalize Cerebral Perfusion Deficits in Mouse Models of Heart Failure and Subarachnoid Hemorrhage

Author

Lidington, Darcy, Fares, Jessica C., Uhl, Franziska E., Dinh, Danny D., Kroetsch, Jeffrey T., Sauvé, Meghan, Malik, Firhan A., Matthes, Frank, Vanherle, Lotte, Adel, Arman, Momen, Abdul, Zhang, Hangjun, Aschar-Sobbi, Roozbeh, Foltz, Warren D., Wan, Hoyee, Sumiyoshi, Manabu, Macdonald, R. Loch, Husain, Mansoor, Backx, Peter H., Heximer, Scott P., Meissner, Anja, and Bolz, Steffen-Sebastian

Published
2019
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21. Common Data Elements for Unruptured Intracranial Aneurysms and Subarachnoid Hemorrhage Clinical Research: A National Institute for Neurological Disorders and Stroke and National Library of Medicine Project

Author

Suarez, Jose I., Sheikh, Muniza K., Macdonald, R. Loch, Amin-Hanjani, Sepideh, Brown, Jr., Robert D., de Oliveira Manoel, Airton Leonardo, Derdeyn, Colin P., Etminan, Nima, Keller, Emanuela, Leroux, Peter D., Mayer, Stephan A., Morita, Akio, Rinkel, Gabriel, Rufennacht, Daniel, Stienen, Martin N., Torner, James, Vergouwen, Mervyn D. I., Wong, George K. C., and the Unruptured Intracranial Aneurysms and SAH CDE Project Investigators

Published
2019
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35. Loss of Consciousness at Onset of Aneurysmal Subarachnoid Hemorrhage is Associated with Functional Outcomes in Good-Grade Patients

Author

Noble, Adam, Molyneux, Andrew, Quinn, Audrey, Schatlo, Bawarjan, Lo, Benjamin, Jaja, Blessing N.R., Johnston, Clay, Hanggi, Daniel, Hasan, David, Wong, George K.C., Lantigua, Hector, Fukuda, Hitoshi, Torner, James, Singh, Jeff, Spears, Julian, Schaller, Karl, Stienen, Martin N., Vergouwen, Mervyn D.I., Cusimano, Michael D., Todd, Michael, Tseng, Ming, Le Roux, Peter, Macdonald, R. Loch, Yamagata, Sen, Mayer, Stephan, Schenk, Thomas, Schweizer, Tom A., Wang, Justin, Alotaibi, Naif M., Akbar, Muhammad Ali, Ayling, Oliver G.S., and Ibrahim, George M.

Published
2017
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36. Predictors of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage with Asymptomatic Angiographic Vasospasm on Admission

Author

Noble, Adam, Molyneux, Andrew, Quinn, Audrey, Schatlo, Bawarjan, Lo, Benjamin, Jaja, Blessing N.R., Johnston, Clay, Hanggi, Daniel, Hasan, David, Wong, George K.C., Lantigua, Hector, Fukuda, Hitoshi, Torner, James, Singh, Jeff, Spears, Julian, Schaller, Karl, Stienen, Martin N., Vergouwen, Mervyn D.I., Cusimano, Michael D., Todd, Michael, Tseng, Ming, Le Roux, Peter, Macdonald, R. Loch, Yamagata, Sen, Mayer, Stephan, Schenk, Thomas, Schweizer, Tom A., Aldakkan, Abdulrahman, Mansouri, Alireza, and Alotaibi, Naif M.

Published
2017
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40. Clinical Trial Protocol: Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study Comparing EG-1962 to Standard of Care Oral Nimodipine in Adults with Aneurysmal Subarachnoid Hemorrhage [NEWTON-2 (Nimodipine Microparticles to Enhance Recovery While Reducing TOxicity After SubarachNoid Hemorrhage)]

Author

Hänggi, Daniel, Etminan, Nima, Mayer, Stephan A., Aldrich, E. Francois, Diringer, Michael N., Schmutzhard, Erich, Faleck, Herbert J., Ng, David, Saville, Benjamin R., Macdonald, R. Loch, and for the NEWTON Investigators

Published
2019
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48. Intrathecal Application of the Nimodipine Slow-Release Microparticle System EG-1962 for Prevention of Delayed Cerebral Ischemia and Improvement of Outcome After Aneurysmal Subarachnoid Hemorrhage

Author

Etminan, Nima, Macdonald, R. Loch, Davis, Cara, Burton, Kevin, Steiger, Hans-Jakob, Hänggi, Daniel, Steiger, Hans-Jakob, Series editor, Fandino, Javier, editor, Marbacher, Serge, editor, Fathi, Ali-Reza, editor, Muroi, Carl, editor, and Keller, Emanuela, editor

Published
2015
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