Growth Hormone Improves Nerve Regeneration, Muscle Re-innervation, and Functional Outcomes After Chronic Denervation Injury

Joseph Lopez, Amy Quan, Joshua Budihardjo, Sinan Xiang, Howard Wang, Koshy Kiron Koshy, Christopher Cashman, W. P.Andrew Lee, Ahmet Hoke, Sami Tuffaha, Gerald Brandacher

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

This study investigates the efficacy of systemic growth hormone (GH) therapy in ameliorating the deleterious effects of chronic denervation (CD) injury on nerve regeneration and resulting motor function. Using a forelimb CD model, 4 groups of Lewis rats were examined (n = 8 per group): Group-1 (negative control) 8 weeks of median nerve CD followed by ulnar-to-median nerve transfer; Group-2 (experimental) 8 weeks of median nerve CD followed by ulnar-to-median nerve transfer and highly purified lyophilized pituitary porcine GH treatment (0.6 mg/day); Group-3 (positive control) immediate ulnar-to-median nerve transfer without CD; Group-4 (baseline) naïve controls. All animals underwent weekly grip strength testing and were sacrificed 14 weeks following nerve transfer for histomorphometric analysis of median nerve regeneration, flexor digitorum superficialis atrophy, and neuromuscular junction reinnervation. In comparison to untreated controls, GH-treated animals demonstrated enhanced median nerve regeneration as measured by axon density (p < 0.005), axon diameter (p < 0.0001), and myelin thickness (p < 0.0001); improved muscle re-innervation (27.9% vs 38.0% NMJs re-innervated; p < 0.02); reduced muscle atrophy (1146 ± 93.19 µm 2 vs 865.2 ± 48.33 µm 2 ; p < 0.02); and greater recovery of motor function (grip strength: p < 0.001). These findings support the hypothesis that GH-therapy enhances axonal regeneration and maintains chronically-denervated muscle to thereby promote motor re-innervation and functional recovery.

Original languageEnglish (US)
Article number3117
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

Fingerprint

Nerve Regeneration
Median Nerve
Denervation
Growth Hormone
Nerve Transfer
Muscles
Wounds and Injuries
Hand Strength
Axons
Muscular Atrophy
Forelimb
Neuromuscular Junction
Recovery of Function
Myelin Sheath
Atrophy
Regeneration
Swine
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

Growth Hormone Improves Nerve Regeneration, Muscle Re-innervation, and Functional Outcomes After Chronic Denervation Injury. / Lopez, Joseph; Quan, Amy; Budihardjo, Joshua; Xiang, Sinan; Wang, Howard; Kiron Koshy, Koshy; Cashman, Christopher; Lee, W. P.Andrew; Hoke, Ahmet; Tuffaha, Sami; Brandacher, Gerald.

In: Scientific reports, Vol. 9, No. 1, 3117, 01.12.2019.

Research output: Contribution to journalArticle

Lopez, J, Quan, A, Budihardjo, J, Xiang, S, Wang, H, Kiron Koshy, K, Cashman, C, Lee, WPA, Hoke, A, Tuffaha, S & Brandacher, G 2019, 'Growth Hormone Improves Nerve Regeneration, Muscle Re-innervation, and Functional Outcomes After Chronic Denervation Injury', Scientific reports, vol. 9, no. 1, 3117. https://doi.org/10.1038/s41598-019-39738-6
Lopez, Joseph ; Quan, Amy ; Budihardjo, Joshua ; Xiang, Sinan ; Wang, Howard ; Kiron Koshy, Koshy ; Cashman, Christopher ; Lee, W. P.Andrew ; Hoke, Ahmet ; Tuffaha, Sami ; Brandacher, Gerald. / Growth Hormone Improves Nerve Regeneration, Muscle Re-innervation, and Functional Outcomes After Chronic Denervation Injury. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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AU - Wang, Howard

AU - Kiron Koshy, Koshy

AU - Cashman, Christopher

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AB - This study investigates the efficacy of systemic growth hormone (GH) therapy in ameliorating the deleterious effects of chronic denervation (CD) injury on nerve regeneration and resulting motor function. Using a forelimb CD model, 4 groups of Lewis rats were examined (n = 8 per group): Group-1 (negative control) 8 weeks of median nerve CD followed by ulnar-to-median nerve transfer; Group-2 (experimental) 8 weeks of median nerve CD followed by ulnar-to-median nerve transfer and highly purified lyophilized pituitary porcine GH treatment (0.6 mg/day); Group-3 (positive control) immediate ulnar-to-median nerve transfer without CD; Group-4 (baseline) naïve controls. All animals underwent weekly grip strength testing and were sacrificed 14 weeks following nerve transfer for histomorphometric analysis of median nerve regeneration, flexor digitorum superficialis atrophy, and neuromuscular junction reinnervation. In comparison to untreated controls, GH-treated animals demonstrated enhanced median nerve regeneration as measured by axon density (p < 0.005), axon diameter (p < 0.0001), and myelin thickness (p < 0.0001); improved muscle re-innervation (27.9% vs 38.0% NMJs re-innervated; p < 0.02); reduced muscle atrophy (1146 ± 93.19 µm 2 vs 865.2 ± 48.33 µm 2 ; p < 0.02); and greater recovery of motor function (grip strength: p < 0.001). These findings support the hypothesis that GH-therapy enhances axonal regeneration and maintains chronically-denervated muscle to thereby promote motor re-innervation and functional recovery.

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