Neural cell injury pathology due to high-rate mechanical loading

Estrada, Jonathan B.; Cramer, Harry C.; Scimone, Mark T.; Buyukozturk, Selda; Franck, Christian

doi:10.1016/j.brain.2021.100034

Cited by 23 publications

(13 citation statements)

References 62 publications

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“…strain rate curve for different RVEs. For the Base RVE (i.e., RVE-1 with

) the failure strain varies between 6.6 and 8.1%, which agrees well with the recent studies that identified the neuronal failure due to Tau is 7.3% ( Estrada et al, 2021 ). The axon can fail much earlier as the MT’s stiffness increases to 1.9 GPa.…”

Section: Resultssupporting

confidence: 88%

“…However, Tau failure is a good indication of the structural damage of the axon cytoskeleton, which can lead to functional damage as well. A recent study showed that axon failed at 7.3% strain via Tau failure when subjected to the loading rate <100/s, which agrees well with the results shown in this work ( Estrada et al, 2021 ). The failure stress is also estimated and varies between 5 and 19.8 MPa.…”

Section: Discussionsupporting

confidence: 92%

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Viscoelastic damage evaluation of the axon

Hasan

Mahmud²,

Khan³

et al. 2022

Front. Bioeng. Biotechnol.

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In this manuscript, we have studied the microstructure of the axonal cytoskeleton and adopted a bottom-up approach to evaluate the mechanical responses of axons. The cytoskeleton of the axon includes the microtubules (MT), Tau proteins (Tau), neurofilaments (NF), and microfilaments (MF). Although most of the rigidity of the axons is due to the MT, the viscoelastic response of axons comes from the Tau. Early studies have shown that NF and MF do not provide significant elasticity to the overall response of axons. Therefore, the most critical aspect of the mechanical response of axons is the microstructural topology of how MT and Tau are connected and construct the cross-linked network. Using a scanning electron microscope (SEM), the cross-sectional view of the axons revealed that the MTs are organized in a hexagonal array and cross-linked by Tau. Therefore, we have developed a hexagonal Representative Volume Element (RVE) of the axonal microstructure with MT and Tau as fibers. The matrix of the RVE is modeled by considering a combined effect of NF and MF. A parametric study is done by varying fiber geometric and mechanical properties. The Young’s modulus and spacing of MT are varied between 1.5 and 1.9 GPa and 20–38 nm, respectively. Tau is modeled as a 3-parameter General Maxwell viscoelastic material. The failure strains for MT and Tau are taken to be 50 and 40%, respectively. A total of 4 RVEs are prepared for finite element analysis, and six loading cases are inspected to quantify the three-dimensional (3D) viscoelastic relaxation response. The volume-averaged stress and strain are then used to fit the relaxation Prony series. Next, we imposed varying strain rates (between 10/sec to 50/sec) on the RVE and analyzed the axonal failure process. We have observed that the 40% failure strain of Tau is achieved in all strain rates before the MT reaches its failure strain of 50%. The corresponding axonal failure strain and stress vary between 6 and 11% and 5–19.8 MPa, respectively. This study can be used to model macroscale axonal aggregate typical of the white matter region of the brain tissue.

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“…strain rate curve for different RVEs. For the Base RVE (i.e., RVE-1 with

Section: Resultssupporting

confidence: 88%

Section: Discussionsupporting

confidence: 92%

Viscoelastic damage evaluation of the axon

Hasan

Mahmud²,

Khan³

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…73,81 It is also known that brain tissue deformations caused by electromagnetic or sonic-based directed energy can occur at high strain rates 4100 s À1 and approach 1000 s À1 . 82,83 Clearly our simulations are in the range of low and moderate strain rates. 82 Because of this, we ran an additional simulation at 30 s À1 strain rate for the highest assumed actin-spectrin association energy of 1.72 eV.…”

Section: Discussionmentioning

confidence: 98%

“…82,83 Clearly our simulations are in the range of low and moderate strain rates. 82 Because of this, we ran an additional simulation at 30 s À1 strain rate for the highest assumed actin-spectrin association energy of 1.72 eV. We observed that at this strain rate all actin-spectrin junctions were dissociated at the very beginning of the simulation.…”

Section: Discussionmentioning

confidence: 98%

Dynamics of the axon plasma membrane skeleton

Chai

Lykotrafitis

2023

Soft Matter

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“…The specific mechanism by which cavitation damages tissue is still unclear, be it bubble collapse, cell membrane interruption, blood-brain barrier disruption, or water jet formation [73]. Although cavitation-induced damage has been measured in brain slices and cell culture systems [74]- [76], there is still a missing link that connects cavitation to fracture. Our study provides this link, using cavitation to initiate fracture in murine brain to report on fracture energies relevant to mild TBI.…”

Section: Discussionmentioning

confidence: 99%