Regenerating and sprouting axons differ in their requirements for growth after injury

Abstract

After spinal cord injury at birth, axotomized brainstem-spinal and corticospinal 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 fetal tissue which is not a normal target of the axotomized neurons (embryonic hippocampus or cortex) is placed into a neonatal spinal cord hemisection, brainstem-spinal serotonergic axons transiently innervate the transplant, but subsequently withdraw. The first set of experiments was designed to test the hypothesis that after spinal cord transection, serotonergic axons would cross the nontarget transplant, reach normal spinal cord targets caudal to the transection, and gain access to requisite target-derived cues, permitting permanent maintenance. Surprisingly, after a complete spinal cord transection, brainstem-spinal axons failed to grow into an inappropriate target even transiently. These observations suggest that the transient axonal ingrowth into nontarget transplants may represent lesion-induced axonal sprouting by contralateral uninjured axons. We have used double-labeling with fluorescent dyes, to test directly whether axonal sprouting of neurons which maintain collaterals to uninjured spinal cord targets (1) provide the transient ingrowth of brainstem-spinal axons into a nontarget transplant and (2) contribute to permanent ingrowth into target-specific transplants. Uninjured red nucleus, raphe nucleus, and locus coeruleus neurons extend axons into the nontarget transplant while maintaining collaterals 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 injury.