Acute implantation of an avulsed lumbosacral ventral root into the rat conus medullaris promotes neuroprotection and graft reinnervation by autonomic and motor neurons

Hoang, Thao X.; Nieto, Juan Antonio Ratón; Dobkin, Bruce H.; Tillakaratne, Niranjala J.K.; Havton, Leif A.

doi:10.1016/j.neuroscience.2005.11.066

Cited by 25 publications

(27 citation statements)

References 58 publications

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“…With the unceasing study of the regeneration capacity of the spinal nerve root axon, [8][9][10][11][12] spinal nerve root microanastomosis has been explored to recover the impaired nerve function in paraplegia patients. Furthermore, some researchers have partially restored muscle and pelvic organs function in paraplegia patients by various surgical procedures, [13][14][15] providing a new therapeutic approach for paraplegia.…”

Section: Discussionmentioning

confidence: 99%

The diameters and number of nerve fibers in spinal nerve roots

Liu

Zhou

et al. 2014

The Journal of Spinal Cord Medicine

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Objective: To investigate the anatomical and histological features of spinal nerve roots and provide base data for neuroanastomosis therapy for paraplegia. Methods: Spinal nerve roots from C1 to S5 were exposed on six adult cadavers. The diameter and the number of nerve fibers of each nerve root were measured, respectively, with a caliper and image analysis software. Results: As for ventral roots, the diameter of C5 (2.50 ± 0.55 mm) was the largest in cervical segments. In thoracic and lumbosacral segments, the diameter gradually increased from T11 to S1 and then decreased from S1 to S5 except L3. S1 (1.43 ± 0.16 mm) was the thickest root and S5 (0.14 ± 0.02 mm) was the thinnest one. As for dorsal roots, the diameter of C7 (4.61 ± 0.87 mm) was the largest in cervical segments. From T11 to S1, the diameter increased and then decreased gradually from S1 to S5. The diameter of dorsal roots from T1 to S5 was largest at S1 (2.95 ± 0.57 mm) and smallest at S5 (0.27 ± 0.13 mm), respectively. C7 (8467 ± 1019), T12 (6538 ± 892), L3 (9169 ± 1160), and S1 (8253 ± 1419) ventral roots contained the most nerve fibers in cervical, thoracic, lumbar, and sacral segments, respectively. Similarly, C7 (39 653 ± 8458), T1 (26 507 ± 7617), L5 (34 455 ± 2740), and S1 (41 543 ± 3036) dorsal roots, respectively, contained the most nerve fibers in their corresponding segments. Conclusion:The findings in the current study provided the imperative data and may be valuable for spinal nerve root microanastomosis surgery in the paraplegic patients.

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Section: Discussionmentioning

confidence: 99%

The diameters and number of nerve fibers in spinal nerve roots

Liu

Zhou

et al. 2014

The Journal of Spinal Cord Medicine

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“…The VRA surgical procedures have been previously described at length (Hoang et al, 2003, Hoang et al, 2006a. Briefly, a midline incision was made along the back under general anesthesia (2% isoflurane).…”

Section: Surgeriesmentioning

confidence: 99%

“…As neuropathic pain is a consequence of this type of spinal cord injury in the clinical setting, we propose that the VRA injury may contribute to the development of neuropathic pain. Further, we propose that a neural repair strategy in which the avulsed roots are reimplanted into the conus medullaris (Hoang et al, 2006a, Hoang, 2006b) may be efficacious in reducing pain after VRA. As reimplantation of the avulsed ventral roots appear to be neuroprotective (Chai et al, 2000, Hoang et al, 2006a) and promotes functional reinnervation of peripheral targets (Carlstedt et al, 1986, Hallin et al, 1999, Gu et al, 2004, Hoang, 2006b, it is vital to also determine whether this translationally relevant neural repair strategy may influence sensory function.…”

Section: Introductionmentioning

confidence: 99%

At-level neuropathic pain is induced by lumbosacral ventral root avulsion injury and ameliorated by root reimplantation into the spinal cord

Bigbee

Hoang

Havton

2007

Experimental Neurology

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Neuropathic pain is common after traumatic injuries to the cauda equina/conus medullaris and brachial plexus. Clinically, this pain is difficult to treat and its mechanisms are not well understood. Lesions to the ventral roots are common in these injuries, but are rarely considered as potential contributors to pain. We examined whether a unilateral L6-S1 ventral root avulsion (VRA) injury in adult female rats might elicit pain within the dermatome projecting to the adjacent, uninjured L5 spinal segment. Additionally, a subset of subjects had the avulsed L6-S1 ventral roots reimplanted (VRA+Imp) into the lateral funiculus post-avulsion to determine whether this neural repair strategy elicits or ameliorates pain. Behavioral tests for mechanical allodynia and hyperalgesia were performed weekly over 7 weeks post-injury at the hind paw plantar surface. Allodynia developed early and persisted post-VRA, whereas VRA+Imp rats exhibited allodynia only at 1 week postoperatively. Hyperalgesia was not observed at any time in any experimental group. Quantitative immunohistochemistry showed increased levels of inflammatory markers in laminae III-V and in the dorsal funiculus of the L5 spinal cord of VRA, but not VRA+Imp rats, specific to areas that receive projections from mechanoreceptive, but not nociceptive, primary afferents. These data suggest that sustained at-level neuropathic pain can develop following a pure motor lesion, whereas the pain may be ameliorated by acute root reimplantation. We believe that our findings are of translational research interest, as root implantation surgery is emerging as a potentially useful strategy for the repair of cauda equina/conus medullaris injuries.

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“…To that end, we have shown that the acute reimplantation repair strategy following a lumbosacral VRA injury facilitates regeneration of efferent axons (Hoang et al, 2006b;Hoang et al, 2006a), reduces neuropathic pain (Bigbee et al, 2007), and here, ameliorates the degeneration of intramedullary afferent projections. By no means, however, is the Imp group completely impervious to the effects of VRA.…”

Section: Reimplantation Of Avulsed Motor Roots Exerts a Prominent Neumentioning

confidence: 99%

“…The result is a progressive and significant death of autonomic and motor neurons at the injured spinal segments, denervation of peripheral targets, and subsequent Wallerian degeneration of the avulsed motor nerve roots (Hoang et al, 2003). Importantly, acute reimplantation of the avulsed roots into the injured spinal segments promotes cell survival, stimulates reinnervation of the implant, and facilitates some physiological restoration of bladder function (Hoang and Havton, 2006;Hoang et al, 2006b;Hoang et al, 2006a).…”

Section: Introductionmentioning

confidence: 99%

Reimplantation of avulsed lumbosacral ventral roots in the rat ameliorates injury-induced degeneration of primary afferent axon collaterals in the spinal dorsal columns

2008

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Injuries to the cauda equina/conus medullaris portion of the spinal cord can result in motor, sensory, and autonomic dysfunction, and neuropathic pain. In rats, unilateral avulsion of the motor efferents from the lumbosacral spinal cord results in at-level allodynia, along with a corresponding glial and inflammatory response in the dorsal horn of the spinal cord segments immediately rostral to the lesion. Here, we investigated the fate of intramedullary primary sensory projections following a motor efferent lesion. The lumbosacral (L6 and S1) ventral roots were unilaterally avulsed from the rat spinal cord (VRA; n=9). A second experimental group had the avulsed roots acutely reimplanted into the lateral funiculus (Imp; n=5), as this neural repair strategy is neuroprotective, and promotes the functional reinnervation of peripheral targets. A laminectomy-only group served as controls (Lam; n=7). At 8 weeks post-lesion, immunohistochemical examination showed a 42% reduction (p<0.001) in the number of RT97-positive axons in the ascending tracts of the dorsal funiculus of the L4-5 spinal segment in VRA rats. Evidence for degenerating myelin was also present. Reimplantation of the avulsed roots ameliorated axon and myelin degeneration. Axons in the descending dorsal corticospinal tract were unaffected in all groups, suggesting a specificity of this lesion for spinal primary sensory afferents. These results show for the first time that a lesion restricted to motor roots can induce the degeneration of intramedullary sensory afferents. Importantly, reimplantation of the lesioned motor roots ameliorated sensory axon degeneration. These data further support the therapeutic potential for reimplantation of avulsed ventral roots following trauma to the cauda equina/conus medullaris.

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Acute implantation of an avulsed lumbosacral ventral root into the rat conus medullaris promotes neuroprotection and graft reinnervation by autonomic and motor neurons

Cited by 25 publications

References 58 publications

The diameters and number of nerve fibers in spinal nerve roots

The diameters and number of nerve fibers in spinal nerve roots

At-level neuropathic pain is induced by lumbosacral ventral root avulsion injury and ameliorated by root reimplantation into the spinal cord

Reimplantation of avulsed lumbosacral ventral roots in the rat ameliorates injury-induced degeneration of primary afferent axon collaterals in the spinal dorsal columns

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