Mechanical properties of glial cells

In recent years, traumatic brain injury (TBI) has received an increase in attention as an “invisible wound”–where mild injuries are difficult to detect non-invasively and remain undiagnosed until postmortem analysis. As most of our knowledge comes from neuropathological evaluation of cellular damage, there is a need for relating the injurious loading to damage at the level of cellular networks. For example, recent analysis of postmortem samples from former football athletes, as well as military personnel, show peculiar damage surrounding arterioles–the small vessels of the arterial vasculature that feed into the capillary bed of the brain. The locations and extent of damage are largely dependent on heterogeneity of brain tissue, which at the length scale of interest ( 1-100 microns), is poorly defined. Glial cells–which encompass astrocytes, oligodendrocytes, and microglia–are con- ventionally believed to comprise the softer “isotropic matrix” which surround axons in previous multiscale models. However, heterogeneity at smaller length scales implies that this might no longer be the case, as the brain appears more as a fibrous network. To simplify the extremely dense and complex structure of brain tissue at the mesoscale, we aim to answer the question, Is there a length scale at which brain tissue constituents have homogeneous mechanical properties? To obtain local mechanical properties of glial cell processes, conventional techniques for obtaining cellular mechanical properties are mostly limited to probing cells grown on 2D substrates, which are shown to provide an unrealistic morphology for glial cells. In order to obtain mechanical properties of glial cell processes with a realistic morphologies, we devised a new experimental platform to probe cellular processes grown in a 3D polymeric scaffold via indentation by optically trapped silica beads. Due to the soft nature of glial cell processes, small forces can generate significantly large deformations–often exceeding the linear elastic regime described by classical Hertzian contact. In light of this observation, we developed a force-displacement relationship for the elliptical contact loading on a hyperelastic cylindrical body. Through our experiments, we demonstrate the glial cells have some mechanical properties that are predominantly homogeneous at small length scales, although their behavior is largely affected by strain-rate. Our findings provide a contribution to our understanding of mesoscale material properties of brain tissue. In the future, we hope this will aid in the development of accurate relationships between the mechanics and neuropathological observations following TBI

The Vehicle, 1969, Vol. 11 no. 2

Vol. 11, No. 2 Table of Contents Short Story: The TripCharles Whitepage 4 PhotoDale Huberpage 5 A NightRoger Zulaufpage 6 Sixteen-year-old Students...NBpage 6 LostJim Biropage 6 The AmateurRoger Zulaufpage 7 ManRoger Zulaufpage 7 My CamelotRonald Garnerpage 7 The Rose and the BriarKenneth L. Folkertspage 9 Who Am I?Frank McKennedypage 10 PhotoDale Huberpage 11 Mr. Samuel ClemensLarry A. Millerpage 11 Lock OutAra Childspage 12 Excuse MeRoger Zulaufpage 12 On Shadows from a Candle \u2767Michael G. McKeepage 12 beginning of an endCaryl Dagropage 12 DrawingMADpage 13 We Ain\u27t Un HurJames Birchlerpage 13 Genesis II, 18 \u2767Michael G. McKeepage 13 Short Story: A Patent Leather PaleEleanor Aikenpage 14 hungry childRoger Zulaufpage 15 DrawingRoger Zulaufpage 15 PhotoRoger Digglepage 16 Do You Like The Rain?Linda Boltmanpage 17 Seasons ChangePerry J. Carterpage 17 PhotoDale Huberpage 19 Whistling TreesPam McKinneypage 19 PostscriptThomas W. Reapage 20 PhotoDale Huberpage 20https://thekeep.eiu.edu/vehicle/1020/thumbnail.jp

The Vehicle, 1969, Vol. 11 no. 2

Vol. 11, No. 2 Table of Contents Short Story: The TripCharles Whitepage 4 PhotoDale Huberpage 5 A NightRoger Zulaufpage 6 Sixteen-year-old Students...NBpage 6 LostJim Biropage 6 The AmateurRoger Zulaufpage 7 ManRoger Zulaufpage 7 My CamelotRonald Garnerpage 7 The Rose and the BriarKenneth L. Folkertspage 9 Who Am I?Frank McKennedypage 10 PhotoDale Huberpage 11 Mr. Samuel ClemensLarry A. Millerpage 11 Lock OutAra Childspage 12 Excuse MeRoger Zulaufpage 12 On Shadows from a Candle \u2767Michael G. McKeepage 12 beginning of an endCaryl Dagropage 12 DrawingMADpage 13 We Ain\u27t Un HurJames Birchlerpage 13 Genesis II, 18 \u2767Michael G. McKeepage 13 Short Story: A Patent Leather PaleEleanor Aikenpage 14 hungry childRoger Zulaufpage 15 DrawingRoger Zulaufpage 15 PhotoRoger Digglepage 16 Do You Like The Rain?Linda Boltmanpage 17 Seasons ChangePerry J. Carterpage 17 PhotoDale Huberpage 19 Whistling TreesPam McKinneypage 19 PostscriptThomas W. Reapage 20 PhotoDale Huberpage 20https://thekeep.eiu.edu/vehicle/1020/thumbnail.jp

Mechanical properties of glial cells

In recent years, traumatic brain injury (TBI) has received an increase in attention as an “invisible wound”–where mild injuries are difficult to detect non-invasively and remain undiagnosed until postmortem analysis. As most of our knowledge comes from neuropathological evaluation of cellular damage, there is a need for relating the injurious loading to damage at the level of cellular networks. For example, recent analysis of postmortem samples from former football athletes, as well as military personnel, show peculiar damage surrounding arterioles–the small vessels of the arterial vasculature that feed into the capillary bed of the brain. The locations and extent of damage are largely dependent on heterogeneity of brain tissue, which at the length scale of interest ( 1-100 microns), is poorly defined. Glial cells–which encompass astrocytes, oligodendrocytes, and microglia–are con- ventionally believed to comprise the softer “isotropic matrix” which surround axons in previous multiscale models. However, heterogeneity at smaller length scales implies that this might no longer be the case, as the brain appears more as a fibrous network. To simplify the extremely dense and complex structure of brain tissue at the mesoscale, we aim to answer the question, Is there a length scale at which brain tissue constituents have homogeneous mechanical properties? To obtain local mechanical properties of glial cell processes, conventional techniques for obtaining cellular mechanical properties are mostly limited to probing cells grown on 2D substrates, which are shown to provide an unrealistic morphology for glial cells. In order to obtain mechanical properties of glial cell processes with a realistic morphologies, we devised a new experimental platform to probe cellular processes grown in a 3D polymeric scaffold via indentation by optically trapped silica beads. Due to the soft nature of glial cell processes, small forces can generate significantly large deformations–often exceeding the linear elastic regime described by classical Hertzian contact. In light of this observation, we developed a force-displacement relationship for the elliptical contact loading on a hyperelastic cylindrical body. Through our experiments, we demonstrate the glial cells have some mechanical properties that are predominantly homogeneous at small length scales, although their behavior is largely affected by strain-rate. Our findings provide a contribution to our understanding of mesoscale material properties of brain tissue. In the future, we hope this will aid in the development of accurate relationships between the mechanics and neuropathological observations following TBI

The percentage of fully degraded edges and percentage of voxels above the 3% threshold for 24, 48, 72, and 96 hrs post-injury.

<p>The percentage of fully degraded edges and percentage of voxels above the 3% threshold for 24, 48, 72, and 96 hrs post-injury.</p

Schematic showing how structural network edges are degraded over time.

<p>Red voxels indicate that the chosen critical cellular death threshold, , is reached. For this study, DTI tracts that traverse a damaged voxel are removed, thus degrading the connection strength of the network edge.</p

Global and local efficiency in terms of time from impact.

<p>Global and local efficiency in terms of time from impact.</p

Changes in (a) total edge strength and (b) global efficiency with change in critical cell death threshold for 24, 48, 72, and 96 hours.

<p>Changes in (a) total edge strength and (b) global efficiency with change in critical cell death threshold for 24, 48, 72, and 96 hours.</p

Orthographic view of the local three-dimensional response measured at various locations in the brain for (a–b) pressure, (c–d) axonal strain and (e–f) strain rate predicted using a finite element simulation for impact to the head.

<p>Prediction of the intracranial pressure response is compared to cadaveric experiments <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002619#pcbi.1002619-Nahum1" target="_blank">[53]</a> and is shown in (b).</p

Combining the Finite Element Method with Structural Connectome-based Analysis for Modeling Neurotrauma: Connectome Neurotrauma Mechanics

<div><p>This article presents the integration of brain injury biomechanics and graph theoretical analysis of neuronal connections, or connectomics, to form a neurocomputational model that captures spatiotemporal characteristics of trauma. We relate localized mechanical brain damage predicted from biofidelic finite element simulations of the human head subjected to impact with degradation in the structural connectome for a single individual. The finite element model incorporates various length scales into the full head simulations by including anisotropic constitutive laws informed by diffusion tensor imaging. Coupling between the finite element analysis and network-based tools is established through experimentally-based cellular injury thresholds for white matter regions. Once edges are degraded, graph theoretical measures are computed on the “damaged” network. For a frontal impact, the simulations predict that the temporal and occipital regions undergo the most axonal strain and strain rate at short times (less than 24 hrs), which leads to cellular death initiation, which results in damage that shows dependence on angle of impact and underlying microstructure of brain tissue. The monotonic cellular death relationships predict a spatiotemporal change of structural damage. Interestingly, at 96 hrs post-impact, computations predict no network nodes were completely disconnected from the network, despite significant damage to network edges. At early times () network measures of global and local efficiency were degraded little; however, as time increased to 96 hrs the network properties were significantly reduced. In the future, this computational framework could help inform functional networks from physics-based structural brain biomechanics to obtain not only a biomechanics-based understanding of injury, but also neurophysiological insight.</p> </div