气候变化领域集成服务门户(CCPortal): Modeling links softening of myelin and spectrin scaffolds of axons after a concussion to increased vulnerability to repeated injuries

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DOI	10.1073/pnas.2024961118
	Modeling links softening of myelin and spectrin scaffolds of axons after a concussion to increased vulnerability to repeated injuries
	Kant A.; Johnson V.E.; Arena J.D.; Dollé J.-P.; Smith D.H.; Shenoy V.B.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:28
英文摘要	Damage to the microtubule lattice, which serves as a rigid cytoskeletal backbone for the axon, is a hallmark mechanical initiator of pathophysiology after concussion. Understanding the mechanical stress transfer from the brain tissue to the axonal cytoskeleton is essential to determine the microtubule lattice's vulnerability to mechanical injury. Here, we develop an ultrastructural model of the axon's cytoskeletal architecture to identify the components involved in the dynamic load transfer during injury. Corroborative in vivo studies were performed using a gyrencephalic swine model of concussion via single and repetitive head rotational acceleration. Computational analysis of the load transfer mechanism demonstrates that the myelin sheath and the actin/spectrin cortex play a significant role in effectively shielding the microtubules from tissue stress. We derive failure maps in the space spanned by tissue stress and stress rate to identify physiological conditions in which the microtubule lattice can rupture. We establish that a softer axonal cortex leads to a higher susceptibility of the microtubules to failure. Immunohistochemical examination of tissue from the swine model of single and repetitive concussion confirms the presence of postinjury spectrin degradation, with more extensive pathology observed following repetitive injury. Because the degradation of myelin and spectrin occurs over weeks following the first injury, we show that softening of the myelin layer and axonal cortex exposes the microtubules to higher stress during repeated incidences of traumatic brain injuries. Our predictions explain how mechanical injury predisposes axons to exacerbated responses to repeated injuries, as observed in vitro and in vivo. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Axonal cytoskeleton damage; Cytoskeletal load transfer mechanism; Repeated traumatic brain injuries
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238871
作者单位	Center for Engineering Mechanobiology, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, PA 19104, United States; Penn Center for Brain Injury and Repair, Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, United States
推荐引用方式 GB/T 7714	Kant A.,Johnson V.E.,Arena J.D.,et al. Modeling links softening of myelin and spectrin scaffolds of axons after a concussion to increased vulnerability to repeated injuries[J],2021,118(28).
APA	Kant A.,Johnson V.E.,Arena J.D.,Dollé J.-P.,Smith D.H.,&Shenoy V.B..(2021).Modeling links softening of myelin and spectrin scaffolds of axons after a concussion to increased vulnerability to repeated injuries.Proceedings of the National Academy of Sciences of the United States of America,118(28).
MLA	Kant A.,et al."Modeling links softening of myelin and spectrin scaffolds of axons after a concussion to increased vulnerability to repeated injuries".Proceedings of the National Academy of Sciences of the United States of America 118.28(2021).