| 1. |
- Georgiadis, Marios, et al.
(författare)
-
Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures.
|
|
| 2. |
- Montanino, Annaclaudia, 1990-, et al.
(författare)
-
Subject-specific multiscale analysis of concussion : from macroscopic loads to molecular-level damage
- 2021
-
Ingår i: Brain Multiphysics. - : Elsevier BV. - 2666-5220. ; 2
-
Tidskriftsartikel (refereegranskat)abstract
- Sports concussion is a form of mild traumatic brain injury (mTBI) caused by an impulsive force transmitted to the head. While concussion is recognized as a complex pathophysiological process affecting the brain at multiple scales, the causal link between external load and cellular, molecular level damage in mTBI remains elusive. The present study proposes a multiscale framework to analyze concussion and demonstrates its applicability with a real-life concussion case. The multiscale analysis starts from inputting mouth guard-recorded head kinematic into a detailed finite element (FE) head model tailored to the subject's head and white matter (WM) tract morphology. The resulting WM tract-oriented strains are then extracted and input to histology-informed micromechanical models of corpus callosum subregions with axonal detail to obtain axolemma strains at a subcellular level. By comparing axolemma strains against mechanoporation thresholds obtained via molecular dynamics (MD) simulations, axonal damage is inferred corresponding to a likelihood of concussion, in line with clinical observation. This novel multiscale framework bridges the organ-to-molecule length scales and accounts both inter- and intra-subject regional variability, providing a new way of non-invasively predicting axonal damage and real-life concussion analysis. The framework may contribute to a better understanding of the mechanistic causes behind concussion. Statement of Significance This study reports a multiscale computational framework for concussion, for the first time revealing a picture of how a global impact to the head measured on the field transfers to the cellular level of axons and finally down to the molecular level. Demonstrated with a real-life concussion case using a detailed and subject-specific head model, the results show molecular level damage corresponds to a likelihood of concussion, in line with clinical observation. An insight into the multiscale mechanical consequences is critical for a better understanding of the complex pathophysiological process affecting the brain at impact, which today are still poorly understood. Analyzing the concussive injury mechanisms the whole way from brains to molecules may also have significant clinical relevance. We show that in a typical injury scenario, the axolemma sustains large enough strains to entail pore formation in the adjoining lipid bilayer. Proration is found to occur in bilayer regions lacking ganglioside lipids, which provides important implications for the treatment of brain injury and other related neurodegenerative diseases.
|
|
| 3. |
- Zhou, Zhou, 1990-, et al.
(författare)
-
The Presence of the Temporal Horn Exacerbates the Vulnerability of Hippocampus During Head Impacts
- 2022
-
Ingår i: Frontiers in Bioengineering and Biotechnology. - : Frontiers Media SA. - 2296-4185. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Hippocampal injury is common in traumatic brain injury (TBI) patients, but the underlying pathogenesis remains elusive. In this study, we hypothesize that the presence of the adjacent fluid-containing temporal horn exacerbates the biomechanical vulnerability of the hippocampus. Two finite element models of the human head were used to investigate this hypothesis, one with and one without the temporal horn, and both including a detailed hippocampal subfield delineation. A fluid-structure interaction coupling approach was used to simulate the brain-ventricle interface, in which the intraventricular cerebrospinal fluid was represented by an arbitrary Lagrangian-Eulerian multi-material formation to account for its fluid behavior. By comparing the response of these two models under identical loadings, the model that included the temporal horn predicted increased magnitudes of strain and strain rate in the hippocampus with respect to its counterpart without the temporal horn. This specifically affected cornu ammonis (CA) 1 (CA1), CA2/3, hippocampal tail, subiculum, and the adjacent amygdala and ventral diencephalon. These computational results suggest that the presence of the temporal horn exacerbate the vulnerability of the hippocampus, highlighting the mechanobiological dependency of the hippocampus on the temporal horn.
|
|
| 4. |
- Zhou, Zhou, et al.
(författare)
-
White matter tract-oriented deformation is dependent on real-time axonal fiber orientation
- 2021
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 38, s. 1730-1745-
-
Tidskriftsartikel (refereegranskat)abstract
- Traumatic axonal injury (TAI) is a critical public health issue with its pathogenesis remaining largely elusive. Finite element (FE) head models are promising tools to bridge the gap between mechanical insult, localized brain response, and resultant injury. In particular, the FE-derived deformation along the direction of white matter (WM) tracts (i.e., tract-oriented strain) has been shown to be an appropriate predictor for TAI. However, the evolution of fiber orientation in time during the impact and its potential influence on the tract-oriented strain remains unknown. To address this question, the present study leveraged an embedded element approach to track real-time fiber orientation during impacts. A new scheme to calculate the tract-oriented strain was proposed by projecting the strain tensors from pre-computed simulations along the temporal fiber direction instead of its static counterpart directly obtained from diffuse tensor imaging. The results revealed that incorporating the real-time fiber orientation not only altered the direction but also amplified the magnitude of the tract-oriented strain, resulting in a generally more extended distribution and a larger volume ratio of WM exposed to high deformation along fiber tracts. These effects were exacerbated with the impact severities characterized by the acceleration magnitudes. Results of this study provide insights into how best to incorporate fiber orientation in head injury models and derive the WM tract-oriented deformation from computational simulations
|
|
