Softening of the chronic hemi-section spinal cord injury scar parallels dysregulation of cellular and extracellular matrix content

Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment

“…Our functional experiments support that SLRPs neither inhibit regeneration through i) direct interactions with the axonal growth cone, nor ii) prevention of inflammation resolution, nor iii) altering the composition of the fibroblastderived injury ECM. Although we cannot exclude that SLRPs influence the availability of neurotrophic factors in the lesion environment, inducing chad, fmod, lum, or prelp expression specifically in neurons did not affect axonal regrowth in vivo, providing evidence Previous studies have shown that CNS injuries in mammals, including humans, are accompanied by a softening of the tissue, whereas the spinal cord of zebrafish stiffens (increased apparent Young's modulus) (9,11,44). This work provides in vivo evidence for a direct relationship between tissue mechanics (longitudinal modulus) and regenerative outcome upon CNS injury.…”

“…Although we cannot exclude that SLRPs influence the availability of neurotrophic factors in the lesion environment, inducing chad, fmod, lum, or prelp expression specifically in neurons did not affect axonal regrowth in vivo, providing evidence against this scenario. accompanied by a softening of the tissue, whereas the spinal cord of zebrafish stiffens (increased apparent Young's modulus)(9,11,44). This work provides in vivo evidence for a direct relationship between tissue mechanics (longitudinal modulus) and regenerative outcome upon CNS injury.…”

“…Previous studies have shown that CNS injuries in mammals, including humans, are accompanied by a softening of the tissue, whereas the spinal cord of zebrafish stiffens (increased apparent Young’s modulus) ( 9, 11, 44 ). This work provides in vivo evidence for a direct relationship between tissue mechanics (longitudinal modulus) and regenerative outcome upon CNS injury.…”

“…However, removing these extracellular matrix (ECM) factors results in only modest regeneration, suggesting that critical molecules and mechanisms contributing to regeneration failure remain to be discovered (6)(7)(8). The CNS scar may inhibit axon growth not only through its biochemical composition, but also by changes in local mechanical properties of the microenvironment (9)(10)(11). However, in vivo evidence for a causal relationship between scar tissue mechanics and regenerative success is lacking.…”

Is Graphene Shortening the Path toward Spinal Cord Regeneration?

“…Taking this into account, mechanical mimicry (in the order of a few kPa, or even lower) must be a key design criterion for electrode systems targeting SCI. It is important to notice that neural tissues typically soften after injury and their endogenous mechanical properties differ according to anatomical features (e.g., white vs gray matters, dura mater). − So, an accurate biomechanical evaluation of the targeted location and adjacent areas should be considered mandatory prior to electrode implantation in order to prevent tissue damage by mechanical mismatch, the withdrawal of neighboring neurons in the electrode surroundings due to tissue swelling and aggressive activation of local astrocyte/microglia toward the formation of a scar tissue encapsulating the probe. , In the long-term, as the distance between the electrode and neuronal cell bodies must not be greater than100 μm for guaranteeing a stable recording, sparse neurons together with the scar barrier effect decisively contributes to isolate the probe from the tissue and increase its electrical impedance …”