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Although most spinal cord injuries are anatomically incomplete, only limited functional recovery has been observed in people and rats with partial lesions. To address why surviving fibers cannot mediate more complete recovery, we evaluated the physiological and anatomical status of spared fibers after unilateral hemisection (HX) of thoracic spinal cord in adult rats. We made intracellular and extracellular recordings at L5 (below HX) in response to electrical stimulation of contralateral white matter above (T6) and below (L1) HX. Responses from T6 displayed reduced amplitude, increased latency and elevated stimulus threshold in the fibers across from HX, beginning 1-2 weeks after HX. Ultrastructural analysis revealed demyelination of intact axons contralateral to the HX, with a time course similar to the conduction changes. Behavioral studies indicated partial recovery which arrested when conduction deficits began. In conclusion, this study is the first demonstration of the delayed decline of transmission through surviving axons to individual lumbar motoneurons during chronic stage of incomplete spinal cord injury in adult rats. These findings suggest a chronic pathological state in intact fibers and necessity for prompt treatment to minimize it.

The aim of this study was to elucidate whether oligodendrocytes die in fiber tracts that are spared by a spinal cord injury but are in close vicinity of inflammatory cells. Adult rat spinal cords were studied histologically 1 day to 2 weeks after a contusion lesion that left the ventral white matter largely intact. Massive oligodendrocyte death occurred in the lesion center, along with the death of neurons, microglia, and astrocytes. Oligodendrocytes, specifically positive for proteolipid protein (PLP) mRNA, were counted in the ventral white matter where axons at the rostral and caudal edges of the lesion were histologically intact. Although these regions contained many macrophages and neutrophils hypothesized to contribute to secondary tissue loss, there was no significant loss of oligodendrocytes. In the ventral funiculus, 3 and 6 mm rostral and caudal to the lesion, oligodendrocyte numbers were also unchanged, in spite of the presence of many activated microglial cells. From day 7 on, oligodendrocytes in close vicinity to the lesion increased their expression of PLP mRNA. We conclude that, at least within the first 2 weeks after a spinal cord contusion lesion, there is no major devastating influence of inflammatory cells or their mediators on oligodendrocytes. When death occurs, it may be due to mechanical trauma, ischemia, or excitotoxicity within the lesion or it may occur as a result of axonal degeneration.

Fetal neocortical transplants placed into adult neocortical sensorimotor aspiration lesions are known to receive afferent input from the adult host rat brain. As this input is less dense than normal, the present study was designed to investigate whether neutralization of myelin-associated neurite growth inhibitors NI-35/250 might promote host derived cholinergic innervation of fetal neocortical transplants. Adult rats received unilateral sensorimotor cortical aspiration lesions, and block grafts from embryonic day 14-15 neocortical tissue were placed immediately into the lesion cavities. Mouse hybridoma cells secreting either the monoclonal antibody IN-1, which blocks neurite growth inhibitors NI-35/250, or a control antibody or medium without cells were applied in millipore filter capsules directly over the fetal graft tissue. The brains were processed 12 weeks later for the visualization of acetylcholinesterase-positive, presumptive cholinergic fibers. We found an enhancement in the cholinergic innervation of fetal grafts in the recipients treated with the antibody IN-1 both in terms of fibers growing into the graft and of density within the center of the grafts. These results indicate that myelin-associated neurite growth inhibitors are involved in the development of host-transplant connectivity in the adult brain.

Lesions of the CNS induce a complex cascade of tissue reactions. The purpose of this study was to determine the response of the vasculature to partial spinal cord transection. Adult rat spinal cords were lesioned and then examined during acute, subacute, and chronic periods for the presence of endothelial cells and blood vessels at the lesion site. The association of endothelial cells and astrocytes was examined immunohistochemically (RECA-1 and glial fibrillary associated protein, respectively). During the first 48 h following an incision lesion of the dorsal spinal cord, the vasculature was significantly decreased, concurrently with the tissue loss due to primary and secondary degeneration. Subsequently, at 4 days postlesion, vasculature repair processes were evidenced by a significant increase in the number of vessels present at the lesion center. Blood vessels even formed in areas densely packed with macrophages and tissue debris. After 1 week, the number of blood vessels declined in the lesion center and at the place of the forming caverns. These results show significant initial attempts at repair of the vasculature which do not, however, lead to the restoration of a compact tissue and cannot prevent the subsequent formation of caverns.