Regeneration of long spinal axons in the rat (original) (raw)
Related papers
Regeneration of descending axon tracts after spinal cord injury
Progress in Neurobiology, 2005
Axons within the adult mammalian central nervous system do not regenerate spontaneously after injury. Upon injury, the balance between growth promoting and growth inhibitory factors in the central nervous system dramatically changes resulting in the absence of regeneration. Axonal responses to injury vary considerably. In central nervous system regeneration studies, the spinal cord has received a lot of attention because of its relatively easy accessibility and its clinical relevance. The present review discusses the axon-tract-specific requirements for regeneration in the rat. This knowledge is very important for the development and optimalization of therapies to repair the injured spinal cord. #
The Journal of Comparative Neurology, 2003
Mice exhibit a unique wound healing response following spinal cord injury in which the lesion site fills in with a connective tissue matrix. Previous studies have revealed that axons grow into this matrix, but the source of the axons remained unknown. The present study assesses whether any of these axons were the result of long tract regeneration. C57Bl/6 mice received crush injuries and were allowed to survive for 6 weeks to 7 months. Biotinylated dextran amine (BDA) was injected into the somato-motor cortex to trace descending corticospinal tract (CST) axons, into the midbrain to label descending brainstem pathways including the rubrospinal and reticulospinal tracts, or into the L5 dorsal root ganglion to trace ascending projections of first-order sensory neurons. Spinal cords from other mice were prepared for immunocytochemistry using antibodies against neurofilament protein (NF), 5-HT to reveal descending serotonergic axons, calcitonin gene-related protein (CGRP) to reveal ascending sensory axons, and chondroitin sulfate proteoglycan (CSPG) to assess the distribution of molecules that are inhibitory to axon growth. NF immunostaining revealed axons in the connective tissue matrix at the lesion site, confirming previous studies that used protargol staining. CST axons did not enter the connective tissue matrix, but did sprout extensively in segments adjacent to the injury site. Rubrospinal and reticulospinal tract axons also did not grow into the lesion site. 5-HT-positive axons extended to the edge of the lesion, and a few axons followed astrocyte processes into the margins of the lesion site. In contrast to the other pathways, BDA-labeled ascending sensory axons did extend into and arborized extensively within the connective tissue matrix, although the subgroup of ascending axons that are positive for CGRP did not. These results indicate that the connective tissue matrix is permissive for regeneration of some classes of ascending sensory axons but not for other axonal systems.
Acta Neurochirurgica, 1986
Autologous sciatic nerve grafts were implanted to the lower thoracic spinal cord (SC) of adult rats. The grafts were longitudinally placed on both sides of the SC midline over the dura mater and their cut ends were inserted into the dorsal white matter of the SC. Eight to 60 weeks later the grafts were exposed. In a first experimental group (A) either horseradish peroxidase (HRP) or lectin conjugated horseradish peroxidase (WGA-HRP) was injected into the grafts in order to investigate the origin and the course of regenerated fibres entering the grafts. In a second experimental group (B) the SC was acutely transected between the upper and lower graft insertions and either HRP or WGA-HRP was injected into the caudal stump of the SC in order to investigate the ability of regenerating axons once entered the grafts to re-enter the SC. In group A retrogradely labelled cells were found in the SC scattered in proximity of both the caudal and rostral graft insertions and in the ventral horns as far as 30 mm rostrally to the grafts. Labelled cells were also located in the spinal ganglia, at the level of the grafts and up to 6 segments caudal to them. In group B retrogradely labelled cells were present in the sC rostrally to the transection, both in proximity of the upper graft insertions and in the ventral horns as far as 30 mm rostrally to the grafts. These findings demonstrate that PN grafts implanted to the SC of adults rats can be innervated by regenerated axons arising from both intraspinal neurons and dorsal root ganglion cells (group A); furthermore axons from intraspinal neurons entered and elongated in the grafts can reenter the SC (group B).
Journal of Neurocytology, 1992
If one end of a segment of peripheral nerve is inserted into the brain or spinal cord, neuronal perikarya in the vicinity of the graft tip can be labelled with retrogradely transported tracers applied to the distal end of the graft several weeks later, showing that CNS axons can regenerate into and along such grafts. We have used transmission EM to examine some of the cellular responses that underlie this regenerative phenomenon, particularly its early stages. Segments of autologous peroneal or tibial nerve were inserted vertically into the thalamus of anaesthetized adult albino rats. The distal end of the graft was left beneath the scalp. Between five days and two months later the animals were killed and the brains prepared for ultrastructural study. Semi-thin and thin sections through the graft and surrounding brain were examined at two levels 6-7 mm apart in all animals: close to the tip of the graft in the thalamus (proximal graft) and at the top of the cerebral cortex (distal graft). In another series of animals with similar grafts, horseradish peroxidase was applied to the distal end of the graft 2448 h before death. Examination by LM of appropriately processed serial coronal sections of the brains from these animals confirmed that up to several hundred neurons were retrogradely labelled in the thalamus, particularly in the thalamic reticular nucleus.
An Ultrastructural Study of the Early Stages of Axonal Regeneration Through Rat Nerve Grafts
Neuropathology and Applied Neurobiology, 1983
An ultrastructural study of the early stages of axonal regeneration through rat nerve grafts Segments of rat sciatic nerve 5 mm long were removed and either maintained alive in tissue culture medium or killed by freeze-drying. Twenty-four h later the nerve segments were replaced as autografts. Animals were killed 3-14 days after grafting. Grafts of cultured nerves (Cgrafts) always contained many living cells. Grafts of freeze-dried nerves (FD-grafts) contained few living cells at 3 days, but were repopulated by 7 days. A few regenerating axons were identified in the most proximal parts of 3 day C-grafts and by 14 days many myelinated axons extended to the distal ends. Axons were absent from 3 and 7 day FD-grafts, but by 14 days some non-myelinated axons extended to the distal end of such grafts. Regenerating axons were always associated with Schwann cells. Small perineurial compartments were formed at the junctional zones of all grafts and throughout the FD-grafts. Revascularization of the FD-grafts was delayed when compared to that in C-grafts. Fenestrated capillaries were observed in both types of graft. These experiments demonstrate that axons regenerate through FD-grafts that have been repopulated by cells and the grafts probably lack the normal perineurial and bloodlnerve diffusion barriers. The significance of these results is discussed in relation to the requirements for successful axonal regeneration.
Neuron, 1999
Absence of a permissive substrate for growth is not, however, the only factor responsible for the failure of Charlestown, Massachusetts 02129 central axons to regenerate (Schwab and Bartholdi, 1996). Three other issues are important: survival of the injured neurons (Coggeshall et al., 1997), the capacity Summary of adult neurons to recapitulate those developmental processes that enable neurite formation and outgrowth, Regeneration is abortive following adult mammalian i.e., their intrinsic growth state (Chong et al., 1996), and, CNS injury. We have investigated whether increasing finally, the formation of impenetrable barriers at the lethe intrinsic growth state of primary sensory neurons sion site (Jakeman and Reier, 1991). by a conditioning peripheral nerve lesion increases Those DRG neurons whose axons ascend in the dorsal regrowth of their central axons. After dorsal column columns provide a useful model system to examine lesions, all fibers stop at the injury site. Animals with central regeneration. First, these cells do not die after a peripheral axotomy concomitant with the central leperipheral or central axonal injury (Coggeshall et al., sion show axonal growth into the lesion but not into 1997). Second, injuring the peripheral but not the centhe spinal cord above the lesion. A preconditioning tral axons of these cells changes their intrinsic growth lesion 1 or 2 weeks prior to the dorsal column injury state (Schreyer and Skene, 1993; Chong et al., 1994). results in growth into the spinal cord above the lesion. This can be seen in vitro where an increased growth In vitro, the growth capacity of DRG neurite is also state can be detected after nerve lesions in dissociated increased following preconditioning lesions. The incells or explant DRG cultures (Hu-Tsai et al., 1994; Edtrinsic growth state of injured neurons is, therefore, a strom et al., 1996; Smith and Skene, 1997). In vivo, induckey determinant for central regeneration. ing peripheral nerve-conditioning lesions at the same time as implanting peripheral nerve grafts immediately adjacent to injured central axons of primary sensory
Journal of Neuroscience, 2008
Studies that have assessed regeneration of corticospinal tract (CST) axons in mice following genetic modifications or other treatments have tacitly assumed that there is little if any regeneration of CST axons in normal mice in the absence of some intervention. Here, we document a previously unrecognized capability for regenerative growth of CST axons in normal mice that involves growth past the lesion via the ventral column. Mice received dorsal hemisection injuries at thoracic level 6-7, which completely transect descending CST axons in the dorsal and dorsolateral column. Corticospinal projections were traced by injecting BDA into the sensorimotor cortex of one hemisphere either at the time of the injury or 4 weeks post-injury, and mice were killed at 20-23 or 46 days post-injury. At 20-23 days post-injury, BDA labeled CST axons did not extend past the lesion except in one animal. By 46 days post-injury, however, a novel population of BDA labeled CST axons could be seen extending from the gray matter rostral to the injury into the ventral column, past the lesion, and then back into the gray matter caudal to the injury where they formed elaborate terminal arbors. The number of axons with this highly unusual trajectory was small (about 1% of the total number of labeled CST axons rostral to the injury). The BDA labeled axons in the ventral column were on the same side as the main tract, and thus are not spared ventral CST axons (which would be contralateral to the main tract). These results indicate that normal mice have a capacity for CST regeneration that has not been previously appreciated, which has important implications in studying the effect of genetic or pharmacological manipulations on CST regeneration in mice.
Journal of the Neurological Sciences, 1987
The pattern of motor axon regeneration following unilateral sciatic nerve lesions (freezing or transection) was studied in adult rats. Transected nerves were repaired with epineurial or fascicular sutures. Four months after the lesion, the motor neuron cell body localization in the spinal cord of plantar or common peroneal nerve axons were examined bilaterally with retrograde transport of horseradish peroxidase. Motor neuron cell body localization was similar bilaterally after freezing, indicating that regenerating axons had reached their original peripheral innervation territory. However, after nerve transection, irrespective of whether epineurial or fascicular sutures were used, motor neuron cell body distribution on the operated side was abnormal with numerous labeled cell bodies located outside the area of the normal motor neuron pool. This finding indicates that after nerve transection the normal pattern of motor axon innervation is not restored even after fascicular nerve repair.