REGENERATING AND SPROUTING AXONS DIFFER IN THEIR REQUIREMENTS FOR GROWTH AFTER INJURY

After spinal cord injury at birth, axotomized brainstem-spinal and cor ticospinal neurons are capable of permanent regenerative axonal growth into and through a fetal spinal cord transplant placed into the site of either a spinal cord hemisection or transection. In contrast, if fe tal tissue which is not a normal target of the axotomized neurons (emb ryonic hippocampus or cortex) is placed into a neonatal spinal cord he misection, brainstem-spinal serotonergic axons transiently innervate t he transplant, but subsequently withdraw. The first set of experiments was designed to test the hypothesis that after spinal cord transectio n, serotonergic axons would cross the nontarget transplant, reach norm al spinal cord targets caudal to the transection, and gain access to r equisite target-derived cues, permitting permanent maintenance. Surpri singly, after a complete spinal cord transection, brainstem-spinal axo ns failed to grow into an inappropriate target even transiently. These observations suggest that the transient axonal ingrowth into nontarge t transplants may represent lesion-induced axonal sprouting by contral ateral uninjured axons. We have used double-labeling with fluorescent dyes, to test directly whether axonal sprouting of neurons which maint ain collaterals to uninjured spinal cord targets (1) provide the trans ient ingrowth of brainstem-spinal axons into a nontarget transplant an d (2) contribute to permanent ingrowth into target-specific transplant s. Uninjured red nucleus, raphe nucleus, and locus coeruleus neurons e xtend axons into the nontarget transplant while maintaining collateral s to the host spinal cord caudal to the transplant. The lesion-induced sprouting by uninjured axons was also observed with a target-specific transplant. Taken together, these studies suggest that sprouting and regenerating axons may differ in their requirements for growth after i njury. (C) 1997 Academic Press.