Reactive glial cells: increased stiffness correlates with increased intermediate filament expression

Lu, Yun-Bi; Iandiev, Ianors; Hollborn, Margrit; Körber, Nicole; Ulbricht, Elke; Hirrlinger, Petra G.; Pannicke, Thomas; Wei, Er-Qing; Bringmann, Andreas; Wolburg, Hartwig; Wilhelmsson, Ulrika; Pekny, Milos; Wiedemann, Peter; Reichenbach, Andreas; Käs, Josef A.

doi:10.1096/fj.10-163790

Cited by 147 publications

(118 citation statements)

References 32 publications

Supporting

Mentioning

113

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, in reeler mice, which lack the extracellular matrix glycoprotein reelin, an increase in the number of glial fibrillary acidic protein (GFAP)-positive astrocytes is accompanied by a decrease in the number of newly generated neurons (Zhao et al, 2007), and enhanced GFAP expression in retinal glial cells leads to their stiffening (Lu et al, 2011). The enhanced GFAP expression in the mouse mutants could thus lead to an increase in tissue stiffness that causes, or at least contributes to, the observed decrease in neurogenesis.…”

Section: Neurogenesismentioning

confidence: 99%

The mechanical control of nervous system development

2013

View full text Add to dashboard Cite

The development of the nervous system has so far, to a large extent, been considered in the context of biochemistry, molecular biology and genetics. However, there is growing evidence that many biological systems also integrate mechanical information when making decisions during differentiation, growth, proliferation, migration and general function. Based on recent findings, I hypothesize that several steps during nervous system development, including neural progenitor cell differentiation, neuronal migration, axon extension and the folding of the brain, rely on or are even driven by mechanical cues and forces.Key words: Mechanics, Mechanosensitivity, Mechanotaxis, Mechanotransduction, Stiffness, Force, Tension, Brain folding Introduction Many processes in development involve growth and motion on different length and time scales. All of these processes are driven by forces; the development of organisms and organ systems would not proceed without mechanics. For example, during neuronal development, neurons migrate and extend immature processes (neurites), which become axons and dendrites. Axons then grow in two different phases, both of which are distinguished by the nature of the forces that drive the growth. In the first phase, growth cones at the tips of axonal processes actively exert forces on their environment (Betz et al., 2011), thus pulling on the processes (Lamoureux et al., 1989). In a second phase, after connecting with their target tissue, axons may be passively pulled by the increasing distance between target and nervous tissue, resulting in considerable growth in length, a process referred to as stretch growth (Weiss, 1941). Once the final connectivity is established, tension may develop along neuronal axons, which may be involved in neuronal network formation and the folding of the brain. Apart from this direct requirement of forces for developmental processes, which has been studied to some degree in the past, the mechanical interaction of cells with their environment may add an additional level of control to several processes in the developing nervous system, including progenitor cell differentiation and cellular guidance.The idea of an important contribution of mechanics to the development of the nervous system has been around for more than a century. However, recent decades have seen only little progress in this field compared with other (e.g. electrophysiology, molecular biology or genetics-based) areas of neuroscience. Progress often depends on the availability of appropriate methodology. Only recently has the increasing involvement of physical and engineering approaches in interdisciplinary studies of biological systems led to the development of new techniques and conceptual approaches that can be used to quantitatively probe and control relevant mechanical parameters, such as cell and tissue stiffness, cellular forces, and tension. In recent years, such tissue mechanics-based studies have resulted in an increasing awareness of the importance of physical parameters, particularly in developm...

show abstract

Section: Neurogenesismentioning

confidence: 99%

The mechanical control of nervous system development

2013

View full text Add to dashboard Cite

show abstract

“…In the retina, the biochemical and biomechanical homeostasis is maintained by Müller cells, which can alter their physical properties through up-or downregulation of intermediary filaments (such as GFAP and vimentin) [11,12,22,23]. This allows Müller cells to control the tissue-wide as well as the cellular biomechanical environment [11,12,22,23].…”

Section: Müller Cell Activationmentioning

confidence: 99%

“…This allows Müller cells to control the tissue-wide as well as the cellular biomechanical environment [11,12,22,23]. In this setting, it is interesting to note that the stiff, intermediary filament-rich Müller cell endfeet contain mechanosensory cation channels, such as TRPV4, which are known to respond to changes in cell membrane stretch through Ca2+ influx [11,12,[22][23][24]. Influx of Ca2+ is a known trigger of intermediary filament upregulation in Müller cells [12,25,26].…”

Section: Müller Cell Activationmentioning

confidence: 99%

In vitro biomechanical modulation—retinal detachment in a box

Ghosh

Arnér

Taylor

2015

Graefes Arch Clin Exp Ophthalmol

View full text Add to dashboard Cite

show abstract

“…At the individual astrocyte level, atomic force microscopy analysis showed that reactive changes in the cytoskeleton, including increased GFAP content, are associated with increased stiffness (that is, increased elasticity) of individual cells. 18 Although the testing method used here offers a very high degree of precision, the numeric values cannot be considered as accurate material property constants. The measured values are intimately related to the details of the testing method.…”

Section: Fig 3 Uppermentioning

confidence: 99%

Intracranial biomechanics following cortical contusion in live rats

Alfasi¹,

Shulyakov

Bigio

2013

JNS

View full text Add to dashboard Cite

Object. The goal of this study was to examine the mechanical properties of living rat intracranial contents and corresponding brain structural alterations following parietal cerebral cortex contusion.Methods. After being anesthetized, young adult rats were subjected to parietal craniotomy followed by cortical contusion using a calibrated weight-drop method. Magnetic resonance imaging was used to visualize the contusion. At the site of contusion, instrumented force-controlled indentation was performed 2 hours to 21 days later on the intact dural surface. The force-deformation (stress-strain) relationship was used to calculate elastic (indentation modulus) and strain changes over time, and constant hold or cyclic stress was used to evaluate viscoelastic deformation. These measurements were followed by histological studies.Results. At contusion sites, the indentation modulus was significantly decreased at 1-3 days and tended to be above control values at 21 days. Multicycle indentation showed that the brain tended to accumulate more strain (an indicator of viscosity) by 1 day after the contusion. Imaging and histological studies showed local edema and hemorrhage at 6 hours to 3 days and accumulation of reactive astrocytes, which began at 3 days and was pronounced by 21 days.Conclusions. The viscoelastic properties of living rat brain change following contusion. Initially, edema and tissue necrosis occur, and the brain becomes less elastic and less viscous. Later, along with undergoing reactive astroglial changes, the brain tends to become stiffer than normal. These quantitative data, which are related to the physical changes in the brain following trauma and which reflect subjective impressions upon palpation, will be useful for understanding emerging diagnostic tools such as magnetic resonance elastography.

show abstract

Reactive glial cells: increased stiffness correlates with increased intermediate filament expression

Cited by 147 publications

References 32 publications

The mechanical control of nervous system development

The mechanical control of nervous system development

In vitro biomechanical modulation—retinal detachment in a box

Intracranial biomechanics following cortical contusion in live rats

Contact Info

Product

Resources

About