Tenascin-R and C in multiple sclerosis lesions: relevance to extracellularmatrix remodelling

In the present study the distribution of the inhibitory extracellular molec ules tenascin-R (TN-R) and tenascin-C (TN-C) was examined by immunocytochem istry during evolution of the multiple sclerosis (MS) lesion, in which astr ogliosis is a prominent feature. Sections were cut from five control cases and from 22 blocks containing lesions representing different pathological s tages in 18 cases of secondary progressive MS. Widespread expression of TN- R was found in the normal human central nervous system (CNS), while that of TN-C was in general restricted to white matter. In acute MS plaques howeve r, there was a similar striking loss of both TN-R and TN-C up to the edge o f the lesion, where the macrophage density is greatest, extending into the apparently normal white matter. In subacute lesions a TN-C and/or TN-R-immu nopositive reactive astrocyte subpopulation was prominent, reflecting synth esis of extracellular matrix molecules. Both tenascins were expressed throu ghout chronic MS plaques at levels similar to those seen in adjacent white matter. The loss of TN-R and TN-C in acute plaques is indicative of enzyme- mediated breakdown of the matrix which may be a marl;er of blood-brain barr ier breakdown and leucocyte extravasation. Subsequent production of tenasci ns by reactive astrocytes may result in glial scar formation impeding remye lination and axonal repair in MS lesions.