TOPICAL GLUCOCORTICOIDS MODULATE THE LESION INTERFACE AFTER CEREBRAL CORTICAL STAB WOUNDS IN ADULT-RATS

A lesion interface, consisting of a glia limitans lined by a laminin-r ich basal lamina and leptomeningeal cells, forms within 2-3 weeks afte r penetrating wounds to the adult mammalian central nervous system (CN S). This interface prevents the growth of axons across the lesion. We have examined the effects of topically applied steroids on the formati on of such an interface after stab wounds to the adult rat cerebral co rtex. Immediately after lesioning, the surface of cortex in the region of the wound was treated with a topical application of either 0.1% ha lcinonide or 0.05% betamethasone dipropionate or their respective plac ebos. Cryostat sections through the lesioned area were obtained 3 week s later and assessed by immunofluorescence. Steroid treatment attenuat ed all components of the lesion. The continuous anti-laminin labeling along the lesion in untreated rats became patchy after steroid treatme nt. The number of leptomeningeal cells that infiltrated into the wound was reduced in the laminin-negative regions in steroid-treated rats. In addition, astrocytic processes in the laminin-negative regions afte r steroid treatment were loosely arranged, compared with the tightly p acked parallel processes forming the glia limitans in laminin-positive regions in controls. The mechanism of steroid-mediated attenuation of the lesion interface was examined in vitro. Betamethasone but not hal cinonide reduced laminin secretion slightly in leptomeningeal cell cul tures, but both steroids reduced cell proliferation. These results sug gest that steroids modulate the formation of the lesion interface afte r CNS injury, at least in part by decreasing leptomeningeal cell proli feration. Such modulation of the lesion interface by steroids or other agents may permit the growth of axons across the lesion site and thus could enhance the overall degree of axon regeneration if other factor s such as neurotrophic support and neutralization of axon growth inhib itory molecules are optimized. (C) 1996 Wiley-Liss, Inc.