The laser lesion of the mouse visual cortex as a model to study neural extracellular matrix remodeling during degeneration, regeneration and plasticity of the CNS

Abstract

CNS lesions generally result in impaired function because regeneration of the adult CNS of mammals is poor. A variety of lesion models has been described that serve to further the understanding of the pathophysiology of the damaged tissue. A central cause of aborted regeneration is the glial scar that expresses a plethora of extracellular matrix molecules. Some of these are considered inhibitors of axon growth and regeneration. The laser lesion of the cortex offers the advantage that a circumscribed lesion of defined energy can be delivered to the cortex non-invasively through the intact dura mater and a thinly drilled wet translucent remnant of the skull. Previously, we have shown that distinct ECM is up-regulated in the penumbra of laser lesions in the rat visual cortex. We propose to transfer this model to the mouse, in view of the availability of a large number of genetical models in this small rodent. Here, we discuss this model and the lesion-related ECM that forms the focus of our analysis.

Influence of the extracellular matrix on endogenous and transplanted stem cells after brain damage

“…Here it was observed that the cells show a specific spatial distribution. For example, focal laser lesions in the adult mouse visual cortex (Roll et al, 2012) induce GFAP upregulation in a wide area, whereas the progenitor markers Vimentin and even more extremely Nestin are restricted to an area near the lesion core (Figure 1). Interestingly, astrocytes (type B cells) are the stem cells of the subventricular zone (SVZ) and are also positive for Nestin and Vimentin (Doetsch et al, 1997, 1999).…”

“…A similar finding of Nestin-expressing cells in a distinct pattern was made in the spinal cord after hemitransection and was also interpreted as local activation (Lang et al, 2004). Re-expression of the ECM molecule TN-C, which is expressed during development and later downregulated in the adult cortex, is also restricted to astrocytes located near the lesion (McKeon et al, 1991; Roll et al, 2012). It can be assumed that gradients of signaling molecules with high concentrations near the lesion and decreasing levels in the periphery influence the cell fate and result in the observed regional differences.…”

“…Depending on the type of damage, the time point after lesion, and the position, reactive astrocytes are responsible for TN-C expression in many lesion models (McKeon et al, 1991; Roll et al, 2012) and also express Brevican, Versican (Beggah et al, 2005), Neurocan (Haas et al, 1999), Phosphacan (McKeon et al, 1999), Decorin (Stichel et al, 1995), Laminin, and FN (Gris et al, 2007). HSPGs expressed by reactive astrocytes are Glypican, Syndecan, and Agrin (Iseki et al, 2002; Hagino et al, 2003; Falo et al, 2008).…”

“…This epitope is expressed on neural stem cells during development (von Holst et al, 2006) and it has been shown that blocking of this epitope impairs neurosphere formation in vitro . Subpopulations of reactive astrocytes after laser lesion in the visual cortex of rats and mice express the DSD-1 epitope (Sirko et al, 2009; Roll et al, 2012). As mentioned above, this might reflect the immature characteristics of some reactive astrocytes and at the same time a neurogenic niche-like signal after CNS damage.…”

Molecular basis of neural repair mechanisms

“…In the first article of this section by Roll et al (2012), a new cortical laser lesion model to investigate remodelling of neural ECM during CNS degeneration, regeneration and plasticity is introduced. The particular advantage of this injury model is the non-invasive mode of cortical lesioning.…”