Diffusion characteristics of beta-aminopropionitrile in peripheral nerve

beta-Aminopropionitrile (beta-APN), a lathyrogen, alters the physical characteristics of fibrous scar tissue and as such may have potential clinical use in treatment of injured spinal cord and peripheral nerve by reducing the physical barrier to axon regeneration. For beta-APN to exert its lathyrogenic effect, it must permeate the injury site and gain access to the developing collagenous scar. To investigate the diffusion characteristics, beta-[14C]APN solution was applied as an immersion bath to rat sciatic nerve using both in vivo and in vitro preparations for intervals of 15 to 90 min. The four experimental groups studied were (a) intact nerve, (b) hemisected nerve, (c) nerve with epineurium removed, and (d) nerve with both epineurium and perineurium removed. The isotope labeling index determined by autoradiography and scintillation counting indicated the perineurium as the primary barrier to significant diffusion of beta-APN in normal nerve. When perineurium was incised or removed, beta-APN entered the endoneurial matrix. beta-APN concentration in the epineurium and perineurium increased with increasing bathing time in vitro; but it decreased markedly after 15 min of in vivo bathing. These findings indicate that topical application of beta-APN to injured peripheral nerve would be a successful method of exposing fibrogenic intraneural tissue to the inhibitory effect on lysyl oxidase enzymes. Continuous application, however, will be necessary because of the rapid beta-APN removal documented in the vivo preparation.