During central nervous system development, gradients of diffusibie mol
ecules play an important role in the attraction of outgrowing axons. A
diffusible tropic factor released by the cervical spinal gray matter
attracts outgrowing corticospinal tract axons, as shown by in vitro co
llagen co-culture studies [Joosten E. A. J. et al. (1994) Neuroscience
59, 33-41]. Here we study the effects of local application of timed c
ervical spinal gray matter extracts on regrowth of injured corticospin
al tract axons in the adult rat spinal cord. For local application of
target-derived extracts at the site of lesion we used rat tail collage
n type 1 as a matrix. Ingrowth of anterogradely labelled corticospinal
tract axons Into the collagen was studied four weeks after the spinal
cord injury. No ingrowth of labelled corticospinal tract axons can be
observed in the control experiment when collagen only was applied int
o the lesion gap. Furthermore, we found that local application of an e
xtract derived from four-day, but not from one-day or 16-day-old, cerv
ical spinal cord gray matter directs a substantial amount of the lesio
ned adult corticospinal tract axons into the collagen implant. We conc
lude that directional regrowth of injured corticospinal tract axons in
the adult rat spinal cord is possible by local application of timed t
arget-derived extracts. In this respect spatiotemporal aspects are of
the utmost importance.