0
Research Papers

Probing Mechanical Properties of Brain in a Tuberous Sclerosis Model of Autism

[+] Author and Article Information
Bo Qing

Department of Biological Engineering,
MIT,
Cambridge, MA 02139

Elizabeth P. Canovic, Anna Jagielska, Matthew J. Whitfield

Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139

Aleksandar S. Mijailovic

Department of Mechanical Engineering,
MIT,
Cambridge, MA 02139

Alexis L. Lowe

Department of Neuroscience,
Wellesley College,
Wellesley, MA 02481

Elyza H. Kelly, Daria Turner, Mustafa Sahin

Department of Neurology,
The F.M. Kirby Neurobiology Center,
Harvard Medical School,
Boston Children's Hospital,
Boston, MA 02115

Krystyn J. Van Vliet

Department of Biological Engineering,
MIT,
Cambridge, MA 02139;
Department of Materials Science
and Engineering,
MIT,
Cambridge, MA 02139
e-mail: krystyn@mit.edu

1B. Qing, E. P. Canovic, and A. S. Mijailovic authors contributed equally.

2Corresponding author.

Manuscript received November 28, 2017; final manuscript received July 12, 2018; published online January 18, 2019. Assoc. Editor: Barclay Morrison.

J Biomech Eng 141(3), 031001 (Jan 18, 2019) (10 pages) Paper No: BIO-17-1558; doi: 10.1115/1.4040945 History: Received November 28, 2017; Revised July 12, 2018

Causes of autism spectrum disorders (ASD) are understood poorly, making diagnosis and treatment challenging. While many studies have investigated the biochemical and genetic aspects of ASD, whether and how mechanical characteristics of the autistic brain can modulate neuronal connectivity and cognition in ASD are unknown. Previously, it has been shown that ASD brains are characterized by abnormal white matter and disorganized neuronal connectivity; we hypothesized that these significant cellular-level structural changes may translate to changes in the mechanical properties of the autistic brain or regions therein. Here, we focused on tuberous sclerosis complex (TSC), a genetic disorder with a high penetrance of ASD. We investigated mechanical differences between murine brains obtained from control and TSC cohorts at various deformation length- and time-scales. At the microscale, we conducted creep-compliance and stress relaxation experiments using atomic force microscope(AFM)-enabled indentation. At the mesoscale, we conducted impact indentation using a pendulum-based instrumented indenter to extract mechanical energy dissipation metrics. At the macroscale, we used oscillatory shear rheology to quantify the frequency-dependent shear moduli. Despite significant changes in the cellular organization of TSC brain tissue, we found no corresponding changes in the quantified mechanical properties at every length- and time-scale explored. This investigation of the mechanical characteristics of the brain has broadened our understanding of causes and markers of TSC/ASD, while raising questions about whether any mechanical differences can be detected in other animal models of ASD or other disease models that also feature abnormal brain structure.

FIGURES IN THIS ARTICLE
<>
Copyright © 2019 by ASME
Your Session has timed out. Please sign back in to continue.

References

Curatolo, P. , Bombardieri, R. , and Jozwiak, S. , 2008, “ Tuberous Sclerosis,” Lancet, 372(9639), pp. 657–668. [CrossRef] [PubMed]
Jeste, S. S. , Sahin, M. , Bolton, P. , Ploubidis, G. B. , and Humphrey, A. , 2008, “ Characterization of Autism in Young Children With Tuberous Sclerosis Complex,” J. Child Neurol., 23(5), pp. 520–525. [CrossRef] [PubMed]
Tsai, P. , and Sahin, M. , 2011, “ Mechanisms of Neurocognitive Dysfunction and Therapeutic Considerations in Tuberous Sclerosis Complex,” Curr. Opin. Neurol., 24(2), pp. 106–113. [CrossRef] [PubMed]
Meikle, L. , Talos, D. M. , Onda, H. , Pollizzi, K. , Rotenberg, A. , Sahin, M. , Jensen, F. E. , and Kwiatkowski, D. J. , 2007, “ A Mouse Model of Tuberous Sclerosis: Neuronal Loss of Tsc1 Causes Dysplastic and Ectopic Neurons, Reduced Myelination, Seizure Activity, and Limited Survival,” J. Neurosci., 27(21), pp. 5546–5558. [CrossRef] [PubMed]
Meikle, L. , Pollizzi, K. , Egnor, A. , Kramvis, I. , Lane, H. , Sahin, M. , and Kwiatkowski, D. J. , 2008, “ Response of a Neuronal Model of Tuberous Sclerosis to Mammalian Target of Rapamycin (mTOR) Inhibitors: Effects on mTORC1 and Akt Signaling Lead to Improved Survival and Function,” J. Neurosci., 28(21), pp. 5422–5432. [CrossRef] [PubMed]
Choi, Y. , Di Nardo, A. , Kramvis, I. , Meikle, L. , Kwiatkowski, D. J. , Sahin, M. , and He, X. , 2008, “ Tuberous Sclerosis Complex Proteins Control Axon Formation,” Genes Develop., 22(18), pp. 2485–2495. [CrossRef]
Nie, D. , Di Nardo, A. , Han, J. M. , Baharanyi, H. , Kramvis, I. , Huynh, T. , Dabora, S. , Codeluppi, S. , Pandolfi, P. , Pasquale, E. , and Sahin, M. , 2010, “ TSC2-Rheb Signaling Regulates EphA-Mediated Axon Guidance,” Nat. Neurosci., 13(2), pp. 163–172. [CrossRef] [PubMed]
Lewis, W. W. , Sahin, M. , Scherrer, B. , Peters, J. M. , Suarez, R. O. , Vogel-Farley, V. K. , Jeste, S. S. , Gregas, M. C. , Prabhu, S. P. , Nelson, C. A. , and Warfield, S. K. , 2013, “ Impaired Language Pathways in Tuberous Sclerosis Complex Patients With Autism Spectrum Disorders,” Cere. Cortex, 23(7), pp. 1526–1532. [CrossRef]
Peters, J. M. , Sahin, M. , Vogel-Farley, V. K. , Jeste, S. S. , Nelson, C. A. , Gregas, M. C. , Prabhu, S. P. , Scherrer, B. , and Warfield, S. K. , 2012, “ Loss of White Matter Microstructural Integrity is Associated With Adverse Neurological Outcome in Tuberous Sclerosis Complex,” Acad. Radiol., 19(1), pp. 17–25. [CrossRef] [PubMed]
Tillema, J. M. , Leach, J. L. , Krueger, D. A. , and Franz, D. N. , 2012, “ Everolimus Alters White Matter Diffusion in Tuberous Sclerosis Complex,” Neurology, 78(8), pp. 526–531. [CrossRef] [PubMed]
van Dommelen, J. A. W. , Hrapko, M. , and Peters, G. W. M. , 2009, “ Mechanical Properties of Brain Tissue: Characterisation and Constitutive Modelling,” Mechanosensitivity of the Nervous System (Mechanosensitivity in Cells and Tissues, Vol. 2), A. Kamkim and I. Kiseleva, eds., Springer, Berlin, pp. 249–279.
Ingber, D. E. , 2003, “ Mechanobiology and Diseases of Mechanotransduction,” Ann. Med., 35(8), pp. 564–577. [CrossRef] [PubMed]
Murphy, M. C. , Huston, J. , Jack, C. R. , Glaser, K. J. , Manduca, A. , Felmlee, J. P. , and Ehman, R. L. , 2012, “ Decreased Brain Stiffness in Alzheimer's Disease Determined by Magnetic Resonance Elastography,” J. Magn. Reson. Imaging, 34(3), pp. 494–498. [CrossRef]
Wuerfel, J. , Paul, F. , Beierbach, B. , Hamhaber, U. , Klatt, D. , Papazoglou, S. , Zipp, F. , Martus, P. , Braun, J. , and Sack, I. , 2010, “ MR-Elastography Reveals Degradation of Tissue Integrity in Multiple Sclerosis,” NeuroImage, 49(3), pp. 2520–2525. [CrossRef] [PubMed]
Riek, K. , Millward, J. M. , Hamann, I. , Mueller, S. , Pfueller, C. F. , Paul, F. , Braun, J. , Infante-Duarte, C. , and Sack, I. , 2012, “ Magnetic Resonance Elastography Reveals Altered Brain Viscoelasticity in Experimental Autoimmune Encephalomyelitis,” NeuroImage. Clin., 1(1), pp. 81–90. [CrossRef] [PubMed]
Liu, F. , and Tschumperlin, D. J. , 2011, “ Micro-Mechanical Characterization of Lung Tissue Using Atomic Force Microscopy,” J. Visualized Exp., (54), p. e2911.
Peaucelle, A. , 2014, “ AFM-Based Mapping of the Elastic Properties of Cell Walls: At Tissue, Cellular, and Subcellular Resolutions,” J. Visualized Exp., (89), p. e51317.
Thomas, G. , Burnham, N. A. , Camesano, T. A. , and Wen, Q. , 2013, “ Measuring the Mechanical Properties of Living Cells Using Atomic Force Microscopy,” J. Visualized Exp., (76), p. e50497.
Moreno-Flores, S. , Benitez, R. , Vivanco, M. D. , and Toca-Herrera, J. L. , 2010, “ Stress Relaxation and Creep on Living Cells With the Atomic Force Microscope: A Means to Calculate Elastic Moduli and Viscosities of Cell Components,” Nanotechnology, 21(44), p. 445101. [CrossRef] [PubMed]
Moreno-Flores, S. , Benitez, R. , Vivanco, M. D. , and Toca-Herrera, J. L. , 2010, “ Stress Relaxation Microscopy: Imaging Local Stress in Cells,” J. Biomech., 43(2), pp. 349–354. [CrossRef] [PubMed]
Desprat, N. , Richert, A. , Simeon, J. , and Asnacios, A. , 2005, “ Creep Function of a Single Living Cell,” Biophys. J., 88(3), pp. 2224–2233. [CrossRef] [PubMed]
Lu, H. , Wang, B. , Ma, J. , Huang, G. , and Viswanathan, H. , 2003, “ Measurement of Creep Compliance of Solid Polymers by Nanoindentation,” Mech. Time-Dependent Mater., 7(3/4), pp. 189–207. [CrossRef]
Cheng, L. , Xia, X. , Scriven, L. E. , and Gerberich, W. W. , 2005, “ Spherical-Tip Indentation of Viscoelastic Material,” Mech. Mater., 37(1), pp. 213–226. [CrossRef]
Kalcioglu, Z. , Qu, M. , and Van Vliet , 2010, “ Multiscale Characterization of Relaxation Times of Tissue Surrogate Gels and Soft Tissues,” Seventh Army Science Conference. http://kjvvgroup.mit.edu/wp-content/uploads/2010/06/27thArmyScienceConferenceManuscript_FP001.pdf
Zhu, Y. , Romero, M. I. , Ghosh, P. , Ye, Z. , Charnay, P. , Rushing, E. J. , Marth, J. D. , and Parada, L. F. , 2001, “ Ablation of NF1 Function in Neurons Induces Abnormal Development of Cerebral Cortex and Reactive Gliosis in the Brain,” Genes Develop., 15(7), pp. 859–876. [CrossRef]
Batra, R. C. , and Jiang, W. , 2008, “ Analytical Solution of the Contact Problem of a Rigid Indenter an Anisotropic Linear Elastic Layer,” Int. J. Solids Struct., 45(22–23), pp. 5814–5830. [CrossRef]
Argatov, I. I. , 2011, “ Depth-Sensing Indentation of a Transversely Isotropic Elastic Layer: Second-Order Asymptotic Models for Conical Indenters,” Int. J. Solids Struct., 48(25–26), pp. 3444–3452. [CrossRef]
Britton, T. B. , Liang, H. , Dunne, F. P. E. , and Wilkinson, A. J. , 2010, “ The Effect of Crystal Orientation on the Indentation Response of Commercially Pure Titanium: Experiments and Simulations,” Proc. R. Soc. A, 466(2115), pp. 695–719. [CrossRef]
Moeendarbary, E. , Weber, I. P. , Sheridan, G. K. , Koser, D. E. , Soleman, S. , Haenzi, B. , Bradbury, E. J. , Fawcett, J. , and Franze, K. , 2017, “ The Soft Mechanical Signature of Glial Scars in the Central Nervous System,” Nat. Commun., 8, p. 14787. [CrossRef] [PubMed]
Canovic, E. P. , Qing, B. , Mijailovic, A. S. , Jagielska, A. , Whitfield, M. J. , Kelly, E. , Turner, D. , Sahin, M. , and Van Vliet, K. J. , 2016, “ Characterizing Multiscale Viscoelastic Properties of Brain Tissue Using Atomic Force Microscopy, Impact Indentation, and Rheometry,” J. Visualized Exp., (115), p. e54201.
Lin, D. C. , Dimitriadis, E. K. , and Horkay, F. , 2007, “ Robust Strategies for Automated AFM Force Curve Analysis-II: Adhesion-Influenced Indentation of Soft, Elastic Materials,” ASME J. Biomech. Eng., 129(6), pp. 904–912. [CrossRef]
Oliver, W. C. , and Pharr, G. M. , 2004, “ Measurement of Hardness and Elastic Modulus by Instrumented Indentation: Advances in Understanding and Refinements to Methodology,” J. Mater. Res., 19(1), pp. 3–20. [CrossRef]
Herbert, E. , Pharr, G. M. , Oliver, W. C. , Lucas, B. N. , and Hay, J. L. , 2001, “ On the Measurement of Stress–Strain Curves by Spherical Indentation,” Thin Solid Films, 398–399, pp. 331–335. [CrossRef]
Lee, E. H. , and Radok, J. R. M. , 1960, “ The Contact Problem for Viscoelastic Bodies,” ASME J. Appl. Mech., 27(3), pp. 438–444. [CrossRef]
Lakes, R. S. , and Wineman, A. , 2006, “ On Poisson's Ratio in Linearly Viscoelastic Solids,” J. Elasticity, 85(1), pp. 45–63. [CrossRef]
Samadi-dooki, A. , Voyiadjis, G. Z. , and Stout, R. W. , 2018, “ A Combined Experimental, Modeling, and Computational Approach to Interpret the Viscoelastic Response of White Matter Brain Tissue During Indentation,” J. Mech. Behav. Biomed. Mater., 77, pp. 24–33. [CrossRef] [PubMed]
Janmey, P. A. , Georges, P. C. , and Hvidt, S. , 2007, “ Basic Rheology for Biologists,” Methods Cell Biol., 83, pp. 3–27. [PubMed]
Mijailovic, A. S. , Qing, B. , Fortunato, D. , and Van Vliet, K. J. , 2018, “ Characterizing Viscoelastic Mechanical Properties of Highly Compliant Polymers and Biological Tissues Using Impact Indentation,” Acta Biomater., 71, pp. 388–397. [CrossRef] [PubMed]
MacManus, D. B. , Pierrat, B. , Murphy, J. G. , and Gilchrist, M. D. , 2017, “ Region and Species Dependent Mechanical Properties of Adolescent and Young Adult Brain Tissue,” Sci. Rep., 7, p. 13729. [CrossRef] [PubMed]
Rashid, B. , Destrade, M. , and Gilchrist, M. D. , 2012, “ Mechanical Characterization of Brain Tissue in Compression at Dynamic Strain Rates,” J. Mech. Behav. Biomed. Mater., 10, pp. 23–38. [CrossRef] [PubMed]
Weickenmeier, J. , de Rooji, R. , Budday, S. , Steinmann, P. , Ovaert, T. C. , and Kuhl, E. , 2016, “ Brain Stiffness Increases With Myelin Content,” Acta Biomater., 42, pp. 265–272. [CrossRef] [PubMed]
Budday, S. , Nay, R. , de Rooji, R. , Steinmann, P. , Wyrobek, T. , Ovaert, T. C. , and Kuhl, E. , 2015, “ Mechanical Properties of Gray and White Matter Brain Tissue by Indentation,” J. Mech. Behav. Biomed. Mater., 46, pp. 318–330. [CrossRef] [PubMed]
Kalcioglu, Z. I. , Qu, M. , Strawhecker, K. E. , Shazly, T. , Edelman, E. , VanLandingham, M. R. , Smith, J. F. , and Van Vliet, K. J. , 2011, “ Dynamic Impact Indentation of Hydrated Biological Tissues and Tissue Surrogate Gels,” Philos. Mag., 91(7–9), pp. 1339–1355. [CrossRef]
Qing, B. , and Van Vliet, K. J. , 2016, “ Hierarchical Design of Synthetic Gel Composites Optimized to Mimic the Impact Energy Dissipation of Brain Tissue,” Mol. Syst. Des. Eng., 1(3), pp. 290–300. [CrossRef]
Finan, J. D. , Fox, P. M. , and Morrison , B., III , 2014, “ Non-Ideal Effects in Indentation Testing of Soft Tissues,” Biomech. Model. Mechanobiol., 13(3), pp. 573–584. [CrossRef] [PubMed]
Constantinides, G. , Kalcioglu, Z. I. , McFarland, M. , Smith, J. F. , and Van Vliet, K. J. , 2008, “ Probing Mechanical Properties of Fully Hydrated Gels and Biological Tissues,” J. Biomech., 41(15), pp. 3285–3289. [CrossRef] [PubMed]
Nicolle, S. , Lounis, M. , and Willinger, R. , 2004, “ Shear Properties of Brain Tissue Over a Frequency Range Relevant for Automotive Impact Situations: New Experimental Results,” Stapp Car Crash J., 48, pp. 239–258. https://www.ncbi.nlm.nih.gov/pubmed/17230269 [PubMed]
Hrapko, M. , van Dommelen, J. A. , Peters, G. W. , and Wismans, J. S. , 2006, “ The Mechanical Behaviour of Brain Tissue: Large Strain Response and Constitutive Modelling,” Biorheology, 43(5), pp. 623–636. [PubMed]
Kalcioglu, Z. I. , Mrozek, R. , Mahmoodian, R. , VanLandingham, M. R. , Lenhart, J. L. , and Van Vliet, K. J. , 2013, “ Tunable Mechanical Behavior of Synthetic Organogels as Biofidelic Tissue Simulants,” J. Biomech., 46(9), pp. 1583–1591. [CrossRef] [PubMed]
Shen, F. , Tay, T. E. , Li, J. Z. , Nigen, S. , Lee, P. V. , and Chan, H. K. , 2006, “ Modified Bilston Nonlinear Viscoelastic Model for Finite Element Head Injury Studies,” ASME J. Biomech. Eng., 128(5), pp. 797–801. [CrossRef]
Pogoda, K. , Chin, L. , Georges, P. C. , Byfield, F. J. , Bucki, R. , Kim, R. , Weaver, M. , Wells, R. G. , Marcinkiewicz, C. , and Janmey, P. A. , 2014, “ Compression Stiffening of Brain and Its Effect on Mechanosensing by Glioma Cells,” New J. Phys., 16(7), p. 075002. [CrossRef] [PubMed]
Stoffels, J. M. , de Jonge, J. C. , Stancic, M. , Nomden, A. , van Strien, M. E. , Ma, D. , Siskova, Z. , Maier, O. , Ffrench-Constant, C. , Franklin, R. J. , Hoekstra, D. , Zhao, C. , and Baron, W. , 2013, “ Fibronectin Aggregation in Multiple Sclerosis Lesions Impairs Remyelination,” Brain, 136(1), pp. 116–131. [CrossRef] [PubMed]
Milner, R. , Crocker, S. J. , Hung, S. , Wang, X. , Frausto, R. F. , and del Zoppor, G. J. , 2007, “ Fibronectin- and Vitronectin-Induced Microglial Activation and Matrix Metalloproteinase-9 Expression Is Mediated by Integrins α5β1 and αvβ5,” J. Immunol., 178(12), pp. 8158–8167. [CrossRef] [PubMed]
Schregel, K. , Wuerfel, E. , Garteiser, P. , Gemeinhardt, I. , Prozorovski, T. , Aktas, O. , Merz, H. , Petersen, D. , Wuerfel, J. , and Sinkus, R. , 2012, “ Demyelination Reduces Brain Parenchymal Stiffness Quantified In Vivo by Magnetic Resonance Elastography,” Proc. Natl. Acad. Sci. U.S.A., 109(17), pp. 6650–6655. [CrossRef] [PubMed]
Uysal, H. , and Hemming, F. W. , 1999, “ Changes in the Expression and Distribution of Fibronectin, Laminin and Tenascin by Cultured Fibroblasts From Skin Lesions of Patients With Tuberous Scleroris,” Br. J. Dermatol., 141(4), pp. 658–666. [CrossRef] [PubMed]
Weickenmeier, J. , de Rooji, R. , Budday, S. , Ovaert, T. C. , and Kuhl, E. , 2017, “ The Mechanical Importance of Myelination in the Central Nervous System,” J. Mech. Behav. Biomed. Mater., 76, pp. 119–124. [CrossRef] [PubMed]
Bush, E. C. , and Allman, J. M. , 2003, “ The Scaling of White Matter to Gray Matter in Cerebellum and Neocortex,” Brain, Behav. Evol., 61(1), pp. 1–5. [CrossRef]
Finan, J. D. , Pearson, E. M. , and Morrison , B., III , 2012, “ Viscoelastic Properties of the Rat Brain in the Horizontal Plane,” IRCOBI Conference, Dublin, Ireland, Sept. 12–14, pp. 474–485. http://www.ircobi.org/wordpress/downloads/irc12/pdf_files/57.pdf
Yoganandan, N. , Pintar, F. A. , Stemper, B. D. , Schlick, M. B. , Philippens, M. , and Wismans, J. , 2000, “ Biomechanics of Human Occupants in Simulated Rear Crashes: Documentation of Neck Injuries and Comparison of Injury Criteria,” Stapp Car Crash J., 44, pp. 189–204. https://www.ncbi.nlm.nih.gov/pubmed/17458727 [PubMed]
Hrapko, M. , van Dommelen, J. A. , Peters, G. W. , and Wismans, J. S. , 2008, “ Characterisation of the Mechanical Behaviour of Brain Tissue in Compression and Shear,” Biorheology, 45(6), pp. 663–676. [PubMed]
Feng, Y. , Okamoto, R. J. , Namani, R. , Genin, G. M. , and Bayly, P. V. , 2013, “ Measurements of Mechanical Anisotropy in Brain Tissue and Implications for Transversely Isotropic Material Models of White Matter,” J. Mech. Behav. Biomed. Mater., 23, pp. 117–132. [CrossRef] [PubMed]
Franze, K. , Janmey, P. A. , and Guck, J. , 2013, “ Mechanics in Neuronal Development and Repair,” Annu. Rev. Biomed. Eng., 15(1), pp. 227–251. [CrossRef] [PubMed]
van Horssen, J. , Dijkstra, C. D. , and de Vries, H. E. , 2007, “ The Extracellular Matrix in Multiple Sclerosis Pathology,” J. Neurochem., 103(4), pp. 1293–301. [CrossRef] [PubMed]
Bonneh-Barkay, D. , and Wiley, C. A. , 2009, “ Brain Extracellular Matrix in Neurodegeneration,” Brain Pathol., 19(4), pp. 573–585. [CrossRef] [PubMed]
Dityatev, A. , Seidenbecher, C. I. , and Schachner, M. , 2010, “ Compartmentalization From the Outside: The Extracellular Matrix and Functional Microdomains in the Brain,” Trends Neurosci., 33(11), pp. 503–512. [CrossRef] [PubMed]
Chatelin, S. , Constantinesco, A. , and Willinger, R. , 2010, “ Fifty Years of Brain Tissue Mechanical Testing: From In Vitro to In Vivo Investigations,” Biorheology, 47(5–6), pp. 255–276. [PubMed]
van Dommelen, J. A. , van der Sande, T. P. , Hrapko, M. , and Peters, G. W. , 2010, “ Mechanical Properties of Brain Tissue by Indentation: Interregional Variation,” J. Mech. Behav. Biomed. Mater., 3(2), pp. 158–166. [CrossRef] [PubMed]
Elkin, B. S. , Ilankovan, A. , and Morrison, B. , 2010, “ Age-Dependent Regional Mechanical Properties of the Rat Hippocampus and Cortex,” ASME J. Biomech. Eng., 132(1), p. 011010. [CrossRef]
Jagielska, A. , Norman, A. L. , Whyte, G. , Van Vliet, K. J. , Guck, J. , and Franklin, R. J. , 2012, “ Mechanical Microenvironment Modulates Biological Properties of Oligodendrocyte Progenitor Cells,” Stem Cells Develop., 21(16), pp. 2905–2914. [CrossRef]
Van Vliet, K. J. , 2010, “ Instrumentation and Experimentation,” Handbook of Nanoindentation, M. Oyen , ed., Pan Stanford, New York, p. 39.
Hardan, A. Y. , Jou, R. J. , Keshavan, M. S. , Varma, R. , and Minshew, N. J. , 2004, “ Increased Frontal Cortical Folding in Austim; A Preliminary MRI Study,” Psychiatr. Res., 131(3), pp. 263–268. [CrossRef]
Nordahl, C. W. , Dierker, D. , Mostafavi, I. , Schumann, C. M. , Rivera, S. M. , Amaral, D. G. , and Van Essen, D. C. , 2007, “ Cortical Folding Abnormalities in Autism Revealed by Surface-Based Morphometry,” J. Neurosci., 27(43), pp. 11725–11735. [CrossRef] [PubMed]
Budday, S. , Steinmann, P. , and Kuhl, E. , 2015, “ Physical Biology of Human Brain Development,” Front. Cellular Neurosci., 9, p. 257. [CrossRef]

Figures

Grahic Jump Location
Fig. 1

Mechanical properties at the micrometer length scale measured using AFM-enabled indentation in the white matter of healthy control and TSC mice: (a) schematic of a coronal section of mouse brain indicating the location of the corpus callosum, (b) the Young's elastic modulus E of TSC brain tissue is not significantly different than that of control tissue, (c) equilibrium modulus E, (d) instantaneous modulus E0, and (e) relaxation time τr obtained from fitting creep (left) and stress relaxation (right) data with a SLS model. These experiments also show no significant differences in any viscoelastic property between the control and TSC brains. Data are represented as mean ± standard deviation (n > 10 measurements per animal; each data point in Fig. 1(b) represents an animal; in Figs. 1(c)–1(e), four control and three TSC animals were characterized for creep and stress relaxation experiments).

Grahic Jump Location
Fig. 2

Impact energy dissipation response metrics of control and TSC mouse brain tissue. (a) maximum penetration depth xmax, (b) energy dissipation capacity K, and (c) dissipation quality factor Q obtained at different impact velocities show no statistical difference between control and TSC brain tissue. Data are represented as mean ± standard deviation (n > 3 measurements per animal; six control and four TSC animals were characterized).

Grahic Jump Location
Fig. 3

Storage G′ moduli (filled symbols) and loss G″ moduli (open symbols) of control and TSC brain tissue at a range of frequencies. Both G′ and G″ show no statistical difference between control and TSC brain tissue for all frequencies measured here. Data are represented as mean ± standard deviation (n = 7 control and 5 TSC mouse brains).

Grahic Jump Location
Fig. 4

Representative images of (a) control and (b) TSC coronal brain slices analyzed for the expression of fibronectin protein (Fn) using fluorescent immunohistochemistry. (c) Mean fluorescence intensity quantified in the original images shows no statistical difference between control and TSC slices. Data are represented as mean ± standard deviation (n = 4 control and five TSC slices).

Tables

Errata

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging and repositioning the boxes below.

Related Journal Articles
Related eBook Content
Topic Collections

Sorry! You do not have access to this content. For assistance or to subscribe, please contact us:

  • TELEPHONE: 1-800-843-2763 (Toll-free in the USA)
  • EMAIL: asmedigitalcollection@asme.org
Sign In