Long‐term changes in the molecular composition of the glial scar and progressive increase of serotoninergic fibre sprouting after hemisection of the mouse spinal cord

Abstract

The scarring process occurring after adult central nervous system injury and the subsequent increase in the expression of certain extracellular matrix molecules are known to contribute to the failure of axon regeneration. This study provides an immunohistochemical analysis of temporal changes (8 days to 1 year) in the cellular and molecular response of the Swiss mouse spinal cord to a dorsal hemisection and its correlation with the axonal growth properties of a descending pathway, the serotoninergic axons. In this lesion model, no cavity forms at the centre of the lesion. Instead, a dense fibronectin-positive tissue matrix occupies the centre of the lesion, surrounded by a glial scar mainly constituted by reactive astrocytes. NG2 proteoglycan and tenascin-C, potential axon growth inhibitors, are constantly associated with the central region. In the glial scar, tenascin-C is never observed and the expression of chondroitin sulphate proteoglycans (revealed with CS-56 and anti-NG2 antibodies) highly increases in the week following injury to progressively return to their control level. In parallel, there is an increasing expression of the polysialilated neural cell adhesion molecule by reactive astrocytes. These molecular changes are correlated with a sprouting process of serotoninergic axons in the glial scar, except in a small area in contact with the central region. All these observations suggest that while a part of the glial scar progressively becomes permissive to axon regeneration after mouse spinal cord injury, the border of the glial scar, in contact with the fibronectin-positive tissue matrix, is the real barrier to prevent axon regeneration.

Delayed Anti-Nogo-A Antibody Application after Spinal Cord Injury Shows Progressive Loss of Responsiveness

“…6C and D). This time course of CSPS expression is in agreement with earlier observations (Camand et al, 2004).…”

Down-regulation of the axonal polysialic acid–neural cell adhesion molecule expression coincides with the onset of myelination in the human fetal forebrain

“…The fact that at midgestation glia cell populations in the human brain do not express PSA-NCAM, as has been shown in rodents, might be due to either inter-species differences or difference in studied stages of development. In addition, astroglial expression of PSA-NCAM reported earlier was related to the reactive astrocytes (Oumesmar et al, 1995;Charles et al, 2002;Camand et al, 2004). It is not unusual that cell adhesion molecules show different patterns of expression during development and in regeneration.…”

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

“…59 Glial scar maturation has been shown to be associated with increased fibronectin deposition, which inhibited axonal growth and healing. 60 Concomitantly, increased fibronectin deposition promoted astrocyte attachment, which played a role in physically separating the injury site from surrounding tissues. 61 Thus, tissue mechanics are critical for normal cellular activities, and when disrupted, tissue function is often impaired.…”