Regeneration of long spinal axons in the rat

Abstract

To investigate regeneration of long spinal axons, the right lateral column of the rat spinal cord was cut at high cervical, low cervical, midthoracic or lumbar level, and one end of an autologous sciatic nerve segment was grafted to the spinal cord at the site of incision. Three to six months after operation, the origin of axons in the grafts was traced retrogradely with horseradish peroxidase injected into the grafts and, in some cases, anterogradely with radioautography of tritiated amino acids injected into the brainstem. Axons from each of the major lateral spinal tracts arising in the brainstem as well as axons ascending from the lower spinal cord succeeded in growing into low cervical grafts. However, long descending axons rarely regenerated after midthoracic or lumbar injury; axons ascending from lumbar segments of the spinal cord usually failed to enter high cervical grafts. Differences in axonal regrowth at the four segmental levels were not simply attributable to dwindling of axonal number in fibre tracts. Axonal regeneration from Clarke's column or the red nucleus was observed only with lesions causing atrophy of many neurons. There was no obvious example of a fibre tract in the lateral spinal columns from which axons failed to regenerate nor from which axons regenerated exceptionally well. Under the conditions of these experiments, the distance from cell body to injury appeared to be an important determinant of axonal regeneration.

Lateral approach of the dog brachial plexus for ventral root reimplantation

“…The grafted rootlets act by providing an environment which appears to be much more permissive to axonal growth and elongation than the surrounding injured CNS tissue of the adult animal. These ®ndings are in full agreement with previous experiments where peripheral nerve grafts (PNG) or roots were implanted into the spinal cord in adult rodents, 3,20 cats, 8 monkeys 9 or dogs. 12 In PNG implantation studies in the dog, the average number of retrogradely HRP labelled cells was about 30.…”

Transplantation strategies to promote repair of the injured spinal cord

“…Most importantly, there was an improved response from brainstem neurons that extended axons over 2 mm onto the bridge and there was, although modest, growth of axons from the bridge into the distal cord. These were both significant findings because the brainstem neurons are distant from the thoracic bridge; it is known that brainstem neurons respond to a peripheral nerve environment only when it is closer to these neuronal somata [23]. Also, the bridge/host interface had apparently been modified to permit the exit of the regenerated fibers.…”

Emergent properties of neural repair: elemental biology to therapeutic concepts

“…Neuronal cell types with the greatest resistance to cell death after injury usually also have the lowest regenerative capacity, such as Purkinje cells, whereas neuronal cell types with the greatest regenerative capacity after injury also suffer the most cell death when injured, such as inferior olivary neurons 64. In neuronal sites as diverse as the optic nerve, dorsal root ganglion, and cortex, lesions closest to the cell body provoke the greatest amount of cell death, but also induce a greater regenerative response—compared to lesions distant from the cell body, in which there is little cell death and also little regeneration 64, 65, 66. Outside of these experimental lesion and molecular observations, increasing the activity of the motor system early after stroke may exacerbate the stroke insult itself in animal models even though this same activity will lead to improved recovery at a later period after stroke 65…”