Increased collateral sprouting of primary afferents in the myelin-free spinal cord

After partial lesions, uninjured nerve fibers have been shown to sprout and expand their connections within the CNS of adult mammals. The extent of this anatomical plasticity in adults is rather limited in comparison to embryonic or neonatal animals. Factors that might limit sprouting of nerve fibers and suppress anatomical plasticity in the CNS include myelin-associated neurite growth inhibitory molecules present in the CNS of adult mammals. To examine further the role of these neurite growth inhibitors, we have studied the ability of primary afferent fibers to sprout in the absence of myelin within a partially deafferented spinal cord. Myelination was suppressed in the lower thoracic and lumbar spinal cord of rats using neonatal x-irradiation. Dorsal roots of lumbar segments L2-L4 were cut in myelin-free and normal spinal cords of 8- or 15-d-old rats. Sprouting of primary afferents was measured after 20 d using thiamine monophosphatase (TMP) histochemistry. TMP is a specific marker enzyme for small-diameter primary afferents that terminate in the substantia gelatinosa (lamina II) of the spinal cord. When compared to the control groups, collateral sprouting of TMP-positive afferents was significantly enhanced in the myelin-free spinal cords: in animals deafferented at postnatal day P8, the average volume occupied by sprouting fibers in the upper dorsal horn was 0.103 mm3 +/- 0.008 (mean +/- SEM) in myelin-free spinal cords and 0.044 mm3 +/- 0.011 in control spinal cords. In spinal cords deafferented at P15, this difference was even larger, with 0.106 mm3 +/- 0.010 in the absence of myelin and 0.031 mm3 +/- 0.010 in controls. Our results indicate that myelin and its associated neurite growth inhibitors restrict collateral sprouting. These data provide further evidence that CNS myelin and its associated neurite growth inhibitors are involved in the regulation of anatomical plasticity in the normal CNS.