Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite Score

Background Because of the failure of numerous clinical trials, various recommendations have been made to improve the usefulness of preclinical studies. Specifically, the STAIR (Stroke Therapy Academic Industry Roundtable) recommendations highlighted functional outcome as a critical measure. Recent r...

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Main Authors: Kanako Matsumura, T. Peeyush Kumar, Tejesh Guddanti, Yuanqing Yan, Spiros L. Blackburn, Devin W. McBride
Format: Article
Language:English
Published: Wiley 2019-04-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.118.011699
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author Kanako Matsumura
T. Peeyush Kumar
Tejesh Guddanti
Yuanqing Yan
Spiros L. Blackburn
Devin W. McBride
author_facet Kanako Matsumura
T. Peeyush Kumar
Tejesh Guddanti
Yuanqing Yan
Spiros L. Blackburn
Devin W. McBride
author_sort Kanako Matsumura
collection DOAJ
description Background Because of the failure of numerous clinical trials, various recommendations have been made to improve the usefulness of preclinical studies. Specifically, the STAIR (Stroke Therapy Academic Industry Roundtable) recommendations highlighted functional outcome as a critical measure. Recent reviews of experimental subarachnoid hemorrhage (SAH) studies have brought to light the numerous neurobehavioral scoring systems that are used in preclinical SAH studies. To gain insight into the utility of these scoring systems, as well as to identify a scoring system that best captures the deficits caused by SAH in mice, we designed the current study. Methods and Results Adult male C57BL/6J mice were used. One cohort of mice was randomly allocated to either sham or SAH and had functional testing performed on days 1 to 3 post‐SAH using the modified Bederson Score, Katz Score, Garcia Neuroscore, and Parra Neuroscore, as well as 21 individual subtests. A new composite neuroscore was developed using the 8 most diagnostically accurate subtests. To validate the use of the developed composite neuroscore, another cohort of mice was randomly assigned to either the sham or SAH group and neurobehavior was evaluated on days 1 to 3, 5, and 7 after injury. Receiver operating characteristic curves were used to analyze the diagnostic accuracy of each scoring system, as well as the subtests. Of the 4 published scoring systems, the Parra Neuroscore was diagnostically accurate for SAH injury in mice versus the modified Bederson and Katz Scores, but not the Garcia Neuroscore. However, the newly developed composite neuroscore was found to be statistically more diagnostically accurate than even the Parra Neuroscore. Conclusions The findings of this study promote use of the newly developed composite neuroscore for experimental SAH studies in mice.
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spelling doaj.art-839af7ea25684063b473c1bb783ef1f52022-12-21T18:13:05ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802019-04-018810.1161/JAHA.118.011699Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite ScoreKanako Matsumura0T. Peeyush Kumar1Tejesh Guddanti2Yuanqing Yan3Spiros L. Blackburn4Devin W. McBride5The Vivian L. Smith Department of Neurosurgery McGovern Medical School The University of Texas Health Science Center at Houston Houston TXThe Vivian L. Smith Department of Neurosurgery McGovern Medical School The University of Texas Health Science Center at Houston Houston TXThe Vivian L. Smith Department of Neurosurgery McGovern Medical School The University of Texas Health Science Center at Houston Houston TXThe Vivian L. Smith Department of Neurosurgery McGovern Medical School The University of Texas Health Science Center at Houston Houston TXThe Vivian L. Smith Department of Neurosurgery McGovern Medical School The University of Texas Health Science Center at Houston Houston TXThe Vivian L. Smith Department of Neurosurgery McGovern Medical School The University of Texas Health Science Center at Houston Houston TXBackground Because of the failure of numerous clinical trials, various recommendations have been made to improve the usefulness of preclinical studies. Specifically, the STAIR (Stroke Therapy Academic Industry Roundtable) recommendations highlighted functional outcome as a critical measure. Recent reviews of experimental subarachnoid hemorrhage (SAH) studies have brought to light the numerous neurobehavioral scoring systems that are used in preclinical SAH studies. To gain insight into the utility of these scoring systems, as well as to identify a scoring system that best captures the deficits caused by SAH in mice, we designed the current study. Methods and Results Adult male C57BL/6J mice were used. One cohort of mice was randomly allocated to either sham or SAH and had functional testing performed on days 1 to 3 post‐SAH using the modified Bederson Score, Katz Score, Garcia Neuroscore, and Parra Neuroscore, as well as 21 individual subtests. A new composite neuroscore was developed using the 8 most diagnostically accurate subtests. To validate the use of the developed composite neuroscore, another cohort of mice was randomly assigned to either the sham or SAH group and neurobehavior was evaluated on days 1 to 3, 5, and 7 after injury. Receiver operating characteristic curves were used to analyze the diagnostic accuracy of each scoring system, as well as the subtests. Of the 4 published scoring systems, the Parra Neuroscore was diagnostically accurate for SAH injury in mice versus the modified Bederson and Katz Scores, but not the Garcia Neuroscore. However, the newly developed composite neuroscore was found to be statistically more diagnostically accurate than even the Parra Neuroscore. Conclusions The findings of this study promote use of the newly developed composite neuroscore for experimental SAH studies in mice.https://www.ahajournals.org/doi/10.1161/JAHA.118.011699basic scienceneurobehaviorneuroscoreoutcomes researchsubarachnoid hemorrhage
spellingShingle Kanako Matsumura
T. Peeyush Kumar
Tejesh Guddanti
Yuanqing Yan
Spiros L. Blackburn
Devin W. McBride
Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite Score
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
basic science
neurobehavior
neuroscore
outcomes research
subarachnoid hemorrhage
title Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite Score
title_full Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite Score
title_fullStr Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite Score
title_full_unstemmed Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite Score
title_short Neurobehavioral Deficits After Subarachnoid Hemorrhage in Mice: Sensitivity Analysis and Development of a New Composite Score
title_sort neurobehavioral deficits after subarachnoid hemorrhage in mice sensitivity analysis and development of a new composite score
topic basic science
neurobehavior
neuroscore
outcomes research
subarachnoid hemorrhage
url https://www.ahajournals.org/doi/10.1161/JAHA.118.011699
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