The effects of protease inhibitors on axon growth through astrocytes

We have shown in a previous paper (Devl Biol. 135, 449, 1989) that axons regenerating from postnatal neurons are unable to penetrate three-dimensional cultures of mature astrocytes, while axons from embryonic dorsal root ganglia (DRGs) and retina will grow through such cultures for considerable distances. We have now investigated the role of proteases in the penetration of three-dimensional astrocyte cultures by axons from embryonic DRGs. Embryonic DRGs were grown in association with three-dimensional astrocyte cultures, with astrocyte monolayers, and with-air dried collagen. The effects of inhibitors of the three families of proteases that have been shown to be involved in tumour cell invasion were investigated. The serine protease inhibitors EACA and Trasylol both reduced growth in three-dimensional astrocyte cultures to around 50% of control, but had little effect on growth on astrocyte monolayers or on collagen. TIMP, which inhibits collagenases, had no effect on growth on two- or three-dimensional cultures. Cbz-gly-phen-amide, an inhibitor of enteroproteases, reduced growth in all three types of culture.