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.