The soft mechanical signature of glial scars in the central nervous system.
Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Mammalian glial scars supposedly form a chemical and mechanical barrier to neuronal regeneration. While tremendous effort has been devoted to identifying molecular characteristics of the scar, very little is known about its mechanical properties. Here we characterize spatiotemporal changes of the elastic stiffness of the injured rat neocortex and spinal cord at 1.5 and three weeks post-injury using atomic force microscopy. In contrast to scars in other mammalian tissues, CNS tissue significantly softens after injury. Expression levels of glial intermediate filaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.|Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave 56, Cambridge, Massachusetts 02139, USA.|Department of Mechanical Engineering, University College London, London WC1E 7JE, UK.
Emad
E
Moeendarbary
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Isabell P
IP
Weber
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.|School of Pharmacy and Biomolecular Sciences, University of Brighton, Lewes Road, Brighton BN2 4GJ, UK.
Graham K
GK
Sheridan
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
David E
0000-0001-6139-3096
DE
Koser
John van Geest Centre for Brain Repair, University of Cambridge, Robinson Way, Cambridge CB2 0PY, UK.
Sara
S
Soleman
John van Geest Centre for Brain Repair, University of Cambridge, Robinson Way, Cambridge CB2 0PY, UK.
Barbara
B
Haenzi
Wolfson Centre for Age-Related Diseases, King's College London, Guy's Campus, London SE1 1UL, UK.
Elizabeth J
EJ
Bradbury
John van Geest Centre for Brain Repair, University of Cambridge, Robinson Way, Cambridge CB2 0PY, UK.
James
J
Fawcett
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Kristian
K
Franze
D000818:Animals; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D024141:Collagen Type IV / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D018625:Microscopy, Atomic Force; D019579:Neocortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014746:Vimentin / Q000378:metabolism
D024141:Collagen Type IV; D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D014746:Vimentin