Residual function after subtotal spinal cord transection in adult cats

Windle, William F.; Smart, J. O.; Beers, Jane J.

doi:10.1212/wnl.8.7.518

Cited by 70 publications

(18 citation statements)

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“…13 The use of peripheral nerve implants and remyelination of the spinal cord with Schwann cells confirmed that only a small proportion of the overall axon population (5%) is sufficient to allow chronic recovery of somatosensory evoked potentials. 7 The use of peripheral nerve implants indicated that partial restoration of hind limb function was possible with a small percentage of regenerating spinal motoneurons.…”

Section: Discussionmentioning

confidence: 86%

Axonal Regeneration in Severed Peripheral Facial Nerve of the Rabbit: Relation of the Number of Axonal Regenerates to Behavioral and Evoked Muscle Activity

Spector

Lee

1998

Ann Otol Rhinol Laryngol

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The minimum number of regenerating facial nerve myelinated motor axons that are required to innervate and activate the mimetic musculature is not known. We compare rabbit facial nerve regeneration following complete transectional injuries of the buccal division to the evoked and behavioral muscle activities of the quadratus labii superioris muscle of the rabbit in three experimental models: end-to-end direct anastomosis (N = 4), 8-mm autologous nerve grafts (N = 8), and 10-mm silicone chamber implants (N = 40). Data are presented as total numbers of regenerating myelinated axons that traverse the surgical repair and innervate the fascicles of the transected distal nerve stump, as well as the percentage of regenerating neurites, as compared to the preoperative normal controls. Five weeks after neural repair, direct end-to-end anastomosis regained more myelinated axons across the reconstructed defect (2,632 +/- 1,232; 67%) than silicone tube implants (2,006 +/- 445; 51%) or autologous cable graft repairs (1,660 +/- 1,169; 42%). However, only a small percentage of myelinated fibers innervated the intrafascicular region of the distal transected neural stump in direct anastomosis (948 +/- 168; 24%), silicone tube implants (670 +/- 275; 17%), or autologous nerve grafts (445 +/- 120; 12%) in rabbits that regained evoked and behavioral mimetic muscle activity. All rabbits with direct anastomosis and neural cable grafts regained motor activity, despite the fact that 66% of regenerating motor neurites in cable graft repairs and 54% in direct anastomosis were collateral sprouts that did not contribute to effective muscle activity. In 17 rabbits with neural regenerates within the silicone tube implants that did not regain mimetic activity, the mean number of regenerating myelinated motor axons across the defect was 504 +/- 419 (13%), and the mean number of axons that innervated the distal transected nerve stump fascicles was 277 +/- 128 (7%). Therefore, the minimal number of motor axons that is required to activate the quadratus labii superioris muscle is 12% of the original motor axon population of the normal buccal nerve division.

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Section: Discussionmentioning

confidence: 86%

Axonal Regeneration in Severed Peripheral Facial Nerve of the Rabbit: Relation of the Number of Axonal Regenerates to Behavioral and Evoked Muscle Activity

Spector

Lee

1998

Ann Otol Rhinol Laryngol

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“…Even very small amounts of remaining ventrolateral white matter were sufficient to initiate locomotion (Windle et al, 1958;Nathan, 1994). At the level of the spinal central pattern-generating network, activity-dependent modifications were recently described (De Leon et al, 1999;Pearson et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Locomotor Recovery in Spinal Cord-Injured Rats Treated with an Antibody Neutralizing the Myelin-Associated Neurite Growth Inhibitor Nogo-A

et al. 2001

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The limited plastic and regenerative capabilities of axons in the adult mammalian CNS can be enhanced by the application of a monoclonal antibody (mAb), IN-1, raised against the myelinassociated neurite growth inhibitor Nogo-A. The aim of the present study was to investigate the effects of this treatment on the functional recovery of adult rats with a dorsal overhemisection of the spinal cord. Directly after injury, half of the animals were implanted with mAb IN-1-secreting hybridoma cells, whereas the others received cells secreting a control antibody (anti-HRP). A broad spectrum of locomotor tests (open field locomotor) score, grid walk, misstep withdrawal response, narrow-beam crossing) was used to characterize locomotor recovery during the 5 weeks after the injury. In all behavioral tests, the recovery in the mAb IN-1-treated group was significantly augmented compared with the control antibodytreated rats. EMG recordings of flexor and extensor muscles during treadmill walking confirmed the improvement of the locomotor pattern in the mAb IN-1-treated rats; step-cycle duration, rhythmicity, and coupling of the hindlimbs were significantly improved. No differences between the two groups with regard to nociception were observed in the tail flick test 5 weeks after the operation. These results indicating improved functional recovery suggest that the increased plastic and regenerative capabilities of the CNS after Nogo-A neutralization result in a functionally meaningful rewiring of the motor systems. Key words: spinal cord injury; functional recovery; locomotion; Nogo-A; regeneration; plasticity; ratsSpontaneous regeneration of injured axons or plastic rearrangements of spared fiber systems after spinal cord injury in mammals are very limited. The major reasons for this poor spontaneous repair capacity seem to be the insufficient growth response of neurons to injury, the growth-inhibitory components of the adult CNS tissue, and the formation of cysts and scar tissue at the injury site. Attempts to overcome local barriers by grafting peripheral nerve bridges (Cheng et al., 1996), Schwann cells (Li and Raisman, 1994;Xu et al., 1995), or olfactory ensheathing cells (Li et al., 1997;Ramon-Cueto et al., 2000) have led to regenerative fiber growth and in some instances to behavioral recovery in animal models of spinal cord injury, although the mechanistic understanding of this recovery remains incomplete because of the complexity of these interventions; Schwann cells and olfactory ensheathing glia are also important sources of trophic factors and extracellular matrix molecules (Guénard et al., 1993;Franklin and Barnett, 2000). Attempts to increase the neuronal growth response by local applications of neurotrophic factors to spinal cord injury sites have led to increased sprouting of CNS fibers and dorsal root axons (Schnell et al., 1994;Grill et al., 1997;Kobayashi et al., 1997;Liu et al., 1999;Ramer et al., 2000). In addition, neutralization of the myelin-associated neurite growth inhibitor Nogo-A (Chen et al., 2000) ...

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“…Depletion experiments through various means demonstrate the detrimental effects of macrophages in the spinal cord and the significant contribution of these cells to tissue damage resulting in expanding central necrotic cavitation in the first weeks after injury (Blight, 1994;Giulian and Robertson 1990;Popovich et al, 1999;Oudega et al, 1999). Even small amounts of tissue preservation may have significant clinical consequence, with evidence that less than 5% white matter sparing produces significant functional recovery in animal models of spinal injury (Basso et al, 1996;Eidelberg et al, 1977;Windle et al, 1958). Attenuating the influx of cytotoxic macrophages may therefore be a clinically useful approach to reduce secondary tissue destruction.…”

Section: Influence Of Macrophages and Microglia On Cns Injurymentioning

confidence: 99%

Comparison of Inflammation in the Brain and Spinal Cord following Mechanical Injury

Batchelor

Tan

Wills

et al. 2008

Journal of Neurotrauma

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Inflammation in the CNS predominantly involves microglia and macrophages, and is believed to be a significant cause of secondary injury following trauma. This study compares the microglial and macrophage response in the rat brain and spinal cord following discrete mechanical injury to better appreciate the degree to which these cells could contribute to secondary damage in these areas. We find that, 1 week after injury, the microglial and macrophage response is significantly greater in the spinal cord compared to the brain. This is the case for injuries to both gray and white matter. In addition, we observed a greater inflammatory response in white matter compared to gray matter within both the brain and spinal cord. Because activated microglia and macrophages appear to be effectors of secondary damage, a greater degree of inflammation in the spinal cord is likely to result in more extensive secondary damage. Tissue saving strategies utilizing anti-inflammatory treatments may therefore be more useful in traumatic spinal cord than brain injury.

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Residual function after subtotal spinal cord transection in adult cats

Cited by 70 publications

References 0 publications

Axonal Regeneration in Severed Peripheral Facial Nerve of the Rabbit: Relation of the Number of Axonal Regenerates to Behavioral and Evoked Muscle Activity

Axonal Regeneration in Severed Peripheral Facial Nerve of the Rabbit: Relation of the Number of Axonal Regenerates to Behavioral and Evoked Muscle Activity

Locomotor Recovery in Spinal Cord-Injured Rats Treated with an Antibody Neutralizing the Myelin-Associated Neurite Growth Inhibitor Nogo-A

Comparison of Inflammation in the Brain and Spinal Cord following Mechanical Injury

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