A re-assessment of the consequences of delayed transplantation of olfactory lamina propria following complete spinal cord transection in rats

Steward, Oswald; Sharp, Kelli; Selvan, Gowri; Hadden, Anthony; Hofstadter, Maura; Au, Edmund; Roskams, Jane

doi:10.1016/j.expneurol.2005.12.034

Cited by 100 publications

(58 citation statements)

References 45 publications

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“…If nogo neutralization influences axonal growth, a more likely mechanism of action may be enhanced sprouting of spared projections (41). Similarly, reports that olfactory ensheathing cells promote corticospinal tract regeneration are the subject of uncertainty (42,43).…”

Section: Discussionmentioning

confidence: 99%

Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation

Hollis

Jamshidi

Löw

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

125

104

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Several experimental manipulations of the CNS environment successfully elicit regeneration of sensory and bulbospinal motor axons but fail to elicit regeneration of corticospinal axons, suggesting that cell-intrinsic mechanisms limit the regeneration of this critical class of motor neurons. We hypothesized that enhancement of intrinsic neuronal growth mechanisms would enable adult corticospinal motor axon regeneration. Lentiviral vectors were used to overexpress the BDNF receptor trkB in layer V corticospinal motor neurons. After subcortical axotomy, trkB transduction induced corticospinal axon regeneration into subcortical lesion sites expressing BDNF. In the absence of trkB overexpression, no regeneration occurred. Selective deletion of canonical, trkB-mediated neurite outgrowth signaling by mutation of the Shc/FRS-2 activation domain prohibited Erk activation and eliminated regeneration. These findings support the hypothesis that the refractory regenerative state of adult corticospinal axons can be attributed at least in part to neuron-intrinsic mechanisms, and that activation of ERK signaling can elicit corticospinal tract regeneration.BDNF ͉ intrinsic ͉ retrograde infection ͉ subcortical lesion

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Section: Discussionmentioning

confidence: 99%

Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation

Hollis

Jamshidi

Löw

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

125

104

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“…The rationale for using these cells in extensive human experimentation now underway is therefore unclear. The rationale for use of these cells in chronic human injury is further limited by a recent report that these cells fail to support functional recovery in rodent models of chronic SCI (Steward et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Lu et al, , 2002Nash et al, 2002;Pascual et al, 2002;Ruitenberg et al, 2002Ruitenberg et al, , 2003Ruitenberg et al, , 2005Takami et al, 2002;Gomez et al, 2003;Keyvan-Fouladi et al, 2003;Plant et al, 2003;Resnick et al, 2003;Verdu et al, 2003;Andrews and Stelzner, 2004;Boyd et al, 2004;Cao et al, 2004;Chuah et al, 2004;Garcia-Alias et al, 2004;Lee et al, 2004;Lopez-Vales et al, 2004Pearse et al, 2004;Polentes et al, 2004;Ramer et al, 2004a,b;Riddell et al, 2004;Sasaki et al, 2004;Barakat et al, 2005;Collazos-Castro et al, 2005;Fouad et al, 2005;Richter et al, 2005;Moreno-Flores et al, 2006). Many of the above studies report that OECs promote axonal regeneration and, in some cases, functional recovery, although controversy exists (Gomez et al, 2003;Ramer et al, 2004b;Riddell et al, 2004;Steward et al, 2006). Nonetheless, cells referred to as OECs have recently been implanted into ϳ1000 human patients with spinal cord injury (Huang et al, 2003;Dobkin et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Olfactory Ensheathing Cells Do Not Exhibit Unique Migratory or Axonal Growth-Promoting Properties after Spinal Cord Injury

Lu¹,

Yang²,

Culbertson³

et al. 2006

J. Neurosci.

114

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Olfactory ensheathing cells (OECs) have been reported to migrate long distances and to bridge lesion sites, guiding axonal regeneration after spinal cord injury (SCI). To understand mechanisms of OEC migration and axonal guidance, we injected lamina propria OECs 1 mm rostral and caudal to C4 SCI sites. One month later, OECs formed an apparent migrating cell tract continuously extending from the injection site through the lesion, physically bridging the lesion. Confocal immunolabeling demonstrated that, whereas this cell tract displaced host astrocytes, descending or ascending long tract axons did not preferentially extend into the cell tract and OECs failed to support bridging of corticospinal axons. Notably, the "bridging" tract of OECs formed within 1 h of cell injection, raising the possibility that cells passively spread from the pressure injection site rather than actively migrating. Control injections of bone marrow stromal cells (MSCs) or fibroblasts 1 mm from the lesion site also rapidly dispersed into the lesion cavity. Cell tracts extending into the lesion site were not seen when cells were injected either at low volumes, into spinal cord gray matter, or 3 d before or 9 d after SCI. OECs proliferated in injection sites, cell tracts, and lesion sites, indicating that OECs can also accumulate through cell proliferation. Thus, OECs do not appear to exhibit significant migratory properties when grafted to the spinal cord, exhibit no detectable difference in promoting axon growth into a SCI site compared with MSCs or fibroblasts, and do not support bridging of corticospinal axons beyond a dorsal column lesion.

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“…Thus, reduction of 5-HT by a complete spinal transection (Clineschmidt et al, 1971;Hadjiconstantinou et al, 1984;Steward et al, 2006) ). For example, in systems disrupted by previous neonatal spinal transection, activation of 5-HT receptors can restore alternating patterned hindlimb behavior (Norreel et al, 2003) and rapidly facilitate stepping ability (but see Kim et al, 1999;Fong et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Changes in Motoneuron Properties and Synaptic Inputs Related to Step Training after Spinal Cord Transection in Rats

Petruska¹,

Ichiyama²,

Jindrich³

et al. 2007

J. Neurosci.

139

116

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Although recovery from spinal cord injury is generally meager, evidence suggests that step training can improve stepping performance, particularly after neonatal spinal injury. The location and nature of the changes in neural substrates underlying the behavioral improvements are not well understood. We examined the kinematics of stepping performance and cellular and synaptic electrophysiological parameters in ankle extensor motoneurons in nontrained and treadmill-trained rats, all receiving a complete spinal transection as neonates. For comparison, electrophysiological experiments included animals injured as young adults, which are far less responsive to training. Recovery of treadmill stepping was associated with significant changes in the cellular properties of motoneurons and their synaptic input from spinal white matter [ipsilateral ventrolateral funiculus (VLF)] and muscle spindle afferents. A strong correlation was found between the effectiveness of step training and the amplitude of both the action potential afterhyperpolarization and synaptic inputs to motoneurons (from peripheral nerve and VLF). These changes were absent if step training was unsuccessful, but other spinal projections, apparently inhibitory to step training, became evident. Greater plasticity of axonal projections after neonatal than after adult injury was suggested by anatomical demonstration of denser VLF projections to hindlimb motoneurons after neonatal injury. This finding confirmed electrophysiological measurements and provides a possible mechanism underlying the greater training susceptibility of animals injured as neonates. Thus, we have demonstrated an "age-at-injury"-related difference that may influence training effectiveness, that successful treadmill step training can alter electrophysiological parameters in the transected spinal cord, and that activation of different pathways may prevent functional improvement.

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A re-assessment of the consequences of delayed transplantation of olfactory lamina propria following complete spinal cord transection in rats

Cited by 100 publications

References 45 publications

Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation

Induction of corticospinal regeneration by lentiviral trkB-induced Erk activation

Olfactory Ensheathing Cells Do Not Exhibit Unique Migratory or Axonal Growth-Promoting Properties after Spinal Cord Injury

Changes in Motoneuron Properties and Synaptic Inputs Related to Step Training after Spinal Cord Transection in Rats

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