Somatotopic Changes in the Nucleus Ambiguus After Section and Regeneration of the Recurrent Laryngeal Nerve of the Rat

Hernández-Morato, Ignacio; Berdugo-Vega, Gabriel; Sañudo, José Ramón; McHanwell, Stephen; Vázquez, Teresa; Valderrama-Canales, Francisco J.; Pascual‐Font, Arán

doi:10.1002/ar.22877

Cited by 14 publications

(17 citation statements)

References 49 publications

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“…The decrease in GFAP immunoreactivity observed in the Amb in the current study at 28 dpi following RLN transection with repair supports the earlier finding that after transection and repair of the RLN, axonal transport recovered between 28 and 56 dpi (Hernández‐Morato et al. ). These results indicate when the axon reaction ceases in the Amb and when the regenerating axons reach their muscle targets.…”

Section: Discussionsupporting

confidence: 91%

“…The latter group was treated as described for the RLN regeneration model of Hernández‐Morato et al. (). For both experimental groups, the RLN was divided at the level of the 6th tracheal cartilage.…”

Section: Methodsmentioning

confidence: 99%

“…The left RLN was then isolated and subjected to either resection of 1 mm (n = 18), or transection or the nerve with immediate repair (n = 19) using surgical fibrin glue (Tissucol Duo, Baxter, Spain). The latter group was treated as described for the RLN regeneration model of Hern andez- Morato et al (2014a). For both experimental groups, the RLN was divided at the level of the 6th tracheal cartilage.…”

Section: Surgical Procedure: Rln Injury and Nerve Tracingmentioning

confidence: 99%

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GFAP immunoreactivity within the rat nucleus ambiguus after laryngeal nerve injury

et al. 2014

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Changes that occur in astroglial populations of the nucleus ambiguus after recurrent (RLN) or superior (SLN) laryngeal nerve injury have hitherto not been fully characterised. In the present study, rat RLN and SLN were lesioned. After 3, 7, 14, 28 or 56 days of survival, the nucleus ambiguus was investigated by means of glial fibrillary acidic protein (GFAP) immunofluorescence or a combination of GFAP immunofluorescence and the application of retrograde tracers. GFAP immunoreactivity was significantly increased 3 days after RLN resection and it remained significantly elevated until after 28 days post injury (dpi). By 56 dpi it had returned to basal levels. In contrast, following RLN transection with repair, GFAP immunoreactivity was significantly elevated at 7 dpi and remained significantly elevated until 14 dpi. It had returned to basal levels by 28 dpi. Topographical analysis of the distribution of GFAP immunoreactivity revealed that after RLN injury, GFAP immunoreactivity was increased beyond the area of the nucleus ambiguus within which RLN motor neuron somata were located. GFAP immunoreactivity was also observed in the vicinity of neuronal somata that project into the uninjured SLN. Similarly, lesion of the SLN resulted in increased GFAP immunoreactivity around the neuronal somata projecting into it and also in the vicinity of the motor neuron somata projecting into the RLN. The increase in GFAP immunoreactivity outside of the region containing the motor neurons projecting into the injured nerve, may reflect the onset of a regenerative process attempting to compensate for impairment of one of the laryngeal nerves and may occur because of the dual innervation of the posterior cricoarytenoid muscle. This dual innervation of a very specialised muscle could provide a useful model system for studying the molecular mechanisms underlying axonal regeneration process and the results of the current study could provide the basis for studies into functional regeneration following laryngeal nerve injury, with subsequent application to humans.

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Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Surgical Procedure: Rln Injury and Nerve Tracingmentioning

confidence: 99%

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GFAP immunoreactivity within the rat nucleus ambiguus after laryngeal nerve injury

et al. 2014

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“…In the rat model following RLN injury, GDNF and Netrin‐1 are upregulated first in the posterior cricoarytenoid muscles (PCA) around 7 DPI and then in the thyroarytenoid muscle (TA) at 14 to 21 DPI. This observed pattern of expression fails to guide the new axons back to their original target . Attempts to alter the concentration of GDNF and Netrin‐1 proteins available within laryngeal muscles resulted in differences in the reinnervation timing when compared to controls but still produced nonselective reinnervation of the larynx.…”

Section: Introductionmentioning

confidence: 99%

Expression of trophic factors receptors during reinnervation after recurrent laryngeal nerve injury

et al. 2019

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Objective: An injury of the recurrent laryngeal nerve (RLN) triggers axonal regeneration but results in a poor functional recovery. Netrin-1 and glial cell-derived neurotrophic factor (GDNF) expression are up-regulated in laryngeal muscles during RLN regeneration, but the role of their receptors produced in the nucleus ambiguus is unknown. The aim of this work was to determine the timing of the production of Netrin-1 and GDNF receptors during RLN regeneration and correlate this with the previously identified timing of up-regulation of their trophic factors in the laryngeal muscles.Study Design: Laboratory experiment with rat model. Methods: The right RLN was transected and dextran amine tracer applied. At 7, 14, and 21 days postinjury (DPI), brainstems were removed and harvested. Immunostaining was performed for Netrin-1 (deleted in colorectal carcinoma [DCC], UNC5A) and GDNF receptors (rearranged during transfection [Ret], glycosylphosphatidylinositol-linked cell surface receptors [GFRα1, GFRα2, GFRα3]). The timing and type of receptor production relative to injury as well as their position in the nucleus ambiguus was analyzed.Results: Netrin-1 UNC5A receptors were minimal in the nucleus ambiguus during RLN regeneration. DCC, the receptor that plays an attract role, was immunopositive from 7 to 21 DPI. All GDNF receptors, except GFRα2, were clearly positive from 7 to 14 DPI. No differences of production were observed according to the position of the motor neurons in the nucleus ambiguus.Conclusion: An injury of the RLN leads to a higher production of Netrin-1 DCC and GDNF receptors in the nucleus ambiguus. The timing of receptor production is similar to up-regulation of their trophic factors in the laryngeal muscles.

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“…As a consequence of an injury to the RLN in rat, the ipsilateral laryngeal fold becomes paralyzed . The injury activates a regenerative state of the nerve with newly sprouting axons from the intact proximal end of the nerve growing toward and reinnervating the denervated laryngeal muscles . Despite the reinnervation, the movement of the vocal folds is never fully restored because of the nonselective synkinetic reinnervation of regenerating axons.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of glial-derived neurotrophic factor in rat laryngeal muscles during reinnervation

et al. 2014

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Differences of GDNF expression are linked to the differential timing of RLN axon regeneration and individual muscle reinnervation. The present finding suggests the need to further investigate the role of GDNF and other neurotrophic factors in the timing of reinnervation, axon guidance, and neuromuscular junction formation as it relates to synkinetic and nonsynkinetic RLN reinnervation. Future experimental results may provide insight to therapeutic options that could stimulate appropriate neuromuscular junction formation and nonsynkintic functional reinnervation following RLN injury.

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Somatotopic Changes in the Nucleus Ambiguus After Section and Regeneration of the Recurrent Laryngeal Nerve of the Rat

Cited by 14 publications

References 49 publications

GFAP immunoreactivity within the rat nucleus ambiguus after laryngeal nerve injury

GFAP immunoreactivity within the rat nucleus ambiguus after laryngeal nerve injury

Expression of trophic factors receptors during reinnervation after recurrent laryngeal nerve injury

Differential expression of glial-derived neurotrophic factor in rat laryngeal muscles during reinnervation

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