NERVE GROWTH-FACTOR PROMOTES REGENERATION OF SENSORY AXONS INTO ADULT-RAT SPINAL-CORD

Injured adult mammalian axons are unable to regenerate spontaneously i n the central nervous tissue. This study investigated in two adult rat models the effects of nerve growth factor (NGF) on the capacity of ce ntral primary sensory axons to regenerate back into the spinal cord. S ensory fibers were conditioned by transection of the peripheral nerve 1 week prior to the experiment and identified by anterograde tracing w ith cholera toxin B subunit injected in the sciatic nerve. In the firs t model, a predegenerated autologous peripheral nerve graft was implan ted as a bridge for the transected sensory fibers into a resection gap in the dorsal columns at the tenth thoracic (T10) spinal cord segment . Vehicle or vehicle with purified mouse or recombinant human NGF was continuously infused for 2 weeks directly into the dorsal column at T9 , 3 mm from the rostral border of the nerve graft. With vehicle infusi on many ascending sensory axons had grown across the nerve bridge, but essentially none had grown back into the rostral cord. fn sharp contr ast, NGF promoted the reentry into the denervated dorsal columns of 51 % of the sensory axons that had reached the rostral level of the nerve graft. Twenty-six percent had grown 2 mm into the spinal tissue and 1 0% had reached the NGF-infusion site at 3 mm from the nerve graft. a f ew fibers were found circling around, but not beyond, the infusion sit e, perhaps due to the chemoattractant action of NGF. In a second model , the fourth lumbar (L4) dorsal root was crushed 2 mm from its inserti on point into the spinal cord and the dorsal roots L2, L3, L5, and L6 were transected. Vehicle or vehicle with purified mouse NGF was infuse d for 2 weeks directly into the lumbar spinal cord, 2.5 mm rostral to the transition zone of the crushed L4 root. With vehicle, only 6% of t he regenerating fibers at the transition zone had crossed the root-spi nal cord barrier, but not farther than 0.5 mm into the spinal tissue. With NGF, 18% of the fibers at the transition zone were found at 0.5 m m, 9% at 1.5 mm, and 5% at 2.5 mm (the infusion site) from the transit ion zone. The present results demonstrate that NGF can promote the reg eneration of adult sensory fibers into the otherwise nonpermissive spi nal cord white matter. (C) 1996 Academic Press, Inc.