Abstract
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.
Highlights
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
Using atomic force microscopy (AFM) indentation experiments, here we show that, in contrast to all other known scars, glial scars in both the rat cortex and spinal cord are softer than healthy CNS tissue
To characterize the mechanical properties of the rat neocortex, we first performed micro-indentation AFM experiments on uninjured coronal brain slices perfused with artificial cerebrospinal fluid (Fig. 1a)
Summary
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. As tissue stiffness is a regulator of neuronal growth, our results may help to understand why mammalian neurons do not regenerate after injury. Glial scars impair axonal outgrowth, which causes aberrant function or death of neurons, leading to devastating consequences such as permanent paralysis of patients after spinal cord injuries. Spinal cord astrocytes adapted their morphology to their mechanical environment[22], while neurons had fewer dendrites but longer axons on softer substrates[23]. The body of evidence for an involvement of mechanical signals in controlling neuronal growth and possibly regeneration, as well as glial cell activation, is continuously growing[28,29]
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