Nerve growth activities in rat peripheral nerve.

Nerve growth activities in rat sciatic nerves were assayed by recording the neuritic outgrowth from chick embryonic ganglia cultured in collagen gels beside nerve fragments for two days. Living nerve explants released activity that resembled nerve growth factor (NGF) in its effect on sympathetic ganglia and that was almost totally blocked by an antiserum to 2.5 S mouse NGF. Frozen and thawed specimens from normal nerves elicited responses from sympathetic ganglia that were only partially suppressed by anti-NGF and also induced neuritic outgrowth from ciliary ganglia. Thus, from observations on normal nerves, at least two agents promoting axonal extension in vitro were deduced to exist; one substance similar to NGF plus another, non-NGF factor. The level of NGF-like activity was low in killed segments of normal nerves but higher in autologous nerve grafts and degenerating nerves two days after grafting or cutting. However, one or two weeks after nerve transection, distal nerve segments contained little nerve growth activity of either kind. Furthermore, when endoneurial fragments from chronically denervated stumps were cultured, they appeared to have lost some of their capacity to produce NGF-like activity in vitro although the production of activity had, if anything, increased in the perineurial region. In summary, rat peripheral nervous tissue releases two or more soluble substances that stimulate neuritic outgrowth. The level of one or both activities in the endoneurium can be altered by manipulation of nerves in vivo.