Growth Hormone Therapy Accelerates Axonal Regeneration, Promotes Motor Reinnervation, and Reduces Muscle Atrophy following Peripheral Nerve Injury

Tuffaha, Sami H.; Budihardjo, Joshua; Sarhane, Karim A.; Khusheim, M.; Song, Diana; Broyles, Justin M.; Salvatori, Roberto; Means, Kenneth R.; Higgins, James P.; Shores, Jaimie T.; Cooney, Damon S.; Höke, Ahmet; Lee, W. P.Andrew; Brandacher, Gerald

doi:10.1097/prs.0000000000002188

Cited by 62 publications

(49 citation statements)

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“…Furthermore, gonadal hormones [ 129 ], like estradiol [ 130 ] and testosterone [ 131 ] contribute increasing axon regeneration after peripheral nerve section. Tuffaha et al [ 132 ] demonstrated that during GH therapy in mice, the peripheral nerve injury accelerates axonal regeneration and myelination, reduces muscle atrophy, and enhances muscle reinnervation. Neuromuscular junction analysis demonstrated a significantly greater percentage of reinnervation of motor endplates in growth hormone-treated animals compared with control.…”

Section: Resultsmentioning

confidence: 99%

Neurotrophic and Neuroregenerative Effects of GH/IGF1

Bianchi¹,

Locatelli

Rizzi

2017

IJMS

150

109

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Introduction. Human neurodegenerative diseases increase progressively with age and present a high social and economic burden. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are both growth factors exerting trophic effects on neuronal regeneration in the central nervous system (CNS) and peripheral nervous system (PNS). GH and IGF-1 stimulate protein synthesis in neurons, glia, oligodendrocytes, and Schwann cells, and favor neuronal survival, inhibiting apoptosis. This study aims to evaluate the effect of GH and IGF-1 on neurons, and their possible therapeutic clinical applications on neuron regeneration in human subjects. Methods. In the literature, we searched the clinical trials and followed up studies in humans, which have evaluated the effect of GH/IGF-1 on CNS and PNS. The following keywords have been used: “GH/IGF-1” associated with “neuroregeneration”, “amyotrophic lateral sclerosis”, “Alzheimer disease”, “Parkinson’s disease”, “brain”, and “neuron”. Results. Of the retrieved articles, we found nine articles about the effect of GH in healthy patients who suffered from traumatic brain injury (TBI), and six studies (four using IGF-1 and two GH therapy) in patients with amyotrophic lateral sclerosis (ALS). The administration of GH in patients after TBI showed a significantly positive recovery of brain and mental function. Treatment with GH and IGF-1 therapy in ALS produced contradictory results. Conclusions. Although strong findings have shown the positive effects of GH/IGF-1 administration on neuroregeneration in animal models, a very limited number of clinical studies have been conducted in humans. GH/IGF-1 therapy had different effects in patients with TBI, evidencing a high recovery of neurons and clinical outcome, while in ALS patients, the results are contradictory. More complex clinical protocols are necessary to evaluate the effect of GH/IGF-1 efficacy in neurodegenerative diseases. It seems evident that GH and IGF-1 therapy favors the optimal recovery of neurons when a consistent residual activity is still present. Furthermore, the effect of GH/IGF-1 could be mediated by, or be overlapped with that of other hormones, such as estradiol and testosterone.

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Section: Resultsmentioning

confidence: 99%

Neurotrophic and Neuroregenerative Effects of GH/IGF1

Bianchi¹,

Locatelli

Rizzi

2017

IJMS

150

109

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“…The femoral nerve is an alternative and suitable model for peripheral nerve injury. Crucial findings regarding nerve regeneration and neurophysiology were revealed with the help of this model (Brushart, ; Brushart, Gerber, Kessens, Chen, & Royall, ; Brushart et al, ; Irintchev et al, ; Kruspe et al, ; Madison, Archibald, & Brushart, ; Madison, Sofroniew, & Robinson, ; Meng et al, ; Robinson & Madison, ; Tuffaha et al, ). Its advantageous features, compared with the sciatic nerve model, include more feasible functional evaluation and absence of limb contractures or automutilation (Irintchev, ; Irintchev et al, ).…”

Section: Discussionmentioning

confidence: 96%

The course of recovery of locomotor function over a 10‐week observation period in a rat model of femoral nerve resection and autograft repair

2020

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Background:A great extent of knowledge on peripheral nerve regeneration has been gathered using the rat sciatic nerve model. The femoral nerve model of the rat offers an interesting alternative, as it lacks disadvantageous features such as automutilation. For the analysis of locomotor behavior in rats after sciatic nerve injury, the CatWalk ™ XT Gait Analysis System is often used. However, lesions of the femoral nerve in the rat have yet remained unstudied with this method. Material and Methods: Ten male Sprague Dawley rats were evaluated with theCatWalk XT to study their gait after a 6-mm resection of the right femoral nerve and reconstruction with an autologous nerve graft. Animals were observed for 10 weeks after surgery.Results: Print Area, Print Length, Swing Speed, and Duty Cycle decreased to a minimum of 40% of baseline 2 weeks after surgery. Swing Time was elevated more than twofold at this time point. However, all these parameters recovered back to >90% of baseline values at 10 weeks after surgery. This degree of functional recovery has not been reported after sciatic nerve resection and autograft repair. Base of support varied minimally postoperatively in contrast to a strong decrement after sciatic nerve resection and repair. Conclusion:We hereby provide a comprehensive in-depth analysis of how to study functional recovery after injury of the femoral nerve in the rat via the CatWalk XT.We place special emphasis on highlighting the differences between the femoral nerve and sciatic nerve injury model in this context. K E Y W O R D SCatWalk XT, femoral nerve, functional recovery, gait analysis, rats, sciatic nerve

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“…Apart from its effects on brain repair after an injury [ 7 , 8 , 9 , 10 , 11 , 12 ], we first reported that GH administration regenerated the transected sciatic nerve in rats [ 13 ], a finding also reported by other authors [ 14 , 15 ]. Unpublished data from our group also indicate that GH and rehabilitation improve the sensitive and motor functions of patients with SC injuries below the level of the spine, at least in ASIA (American Spinal Cord Injury Association) B and C patients [ 16 ].…”

Section: Introductionmentioning

confidence: 63%

“…We and others have demonstrated [ 13 , 14 , 15 ] in rats that early GH treatment is able to recover sciatic nerve transection, increasing the number of Schwann cells that produce myelin, promoting axonal regeneration and muscle reinnervation; consequently, the affected muscles recover their trophism. This, and our unpublished studies in patients with SC injuries [ 16 ], indicates that GH is able to promote peripheral axonal growth, and this might explain the effect of the hormone on the innervation observed in our CSR patient.…”

Section: Discussionmentioning

confidence: 99%

Growth Hormone (GH) and Rehabilitation Promoted Distal Innervation in a Child Affected by Caudal Regression Syndrome

Devesa¹,

Alonso²,

López³

et al. 2017

IJMS

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Caudal regression syndrome (CRS) is a malformation occurring during the fetal period and mainly characterized by an incomplete development of the spinal cord (SC), which is often accompanied by other developmental anomalies. We studied a 9-month old child with CRS who presented interruption of the SC at the L2–L3 level, sacral agenesis, a lack of innervation of the inferior limbs (flaccid paraplegia), and neurogenic bladder and bowel. Given the known positive effects of growth hormone (GH) on neural stem cells (NSCs), we treated him with GH and rehabilitation, trying to induce recovery from the aforementioned sequelae. The Gross Motor Function Test (GMFM)-88 test score was 12.31%. After a blood analysis, GH treatment (0.3 mg/day, 5 days/week, during 3 months and then 15 days without GH) and rehabilitation commenced. This protocol was followed for 5 years, the last GH dose being 1 mg/day. Blood analysis and physical exams were performed every 3 months initially and then every 6 months. Six months after commencing the treatment the GMFM-88 score increased to 39.48%. Responses to sensitive stimuli appeared in most of the territories explored; 18 months later sensitive innervation was complete and the patient moved all muscles over the knees and controlled his sphincters. Three years later he began to walk with crutches, there was plantar flexion, and the GMFM-88 score was 78.48%. In summary, GH plus rehabilitation may be useful for innervating distal areas below the level of the incomplete spinal cord in CRS. It is likely that GH acted on the ependymal SC NSCs, as the hormone does in the neurogenic niches of the brain, and rehabilitation helped to achieve practically full functionality.

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Growth Hormone Therapy Accelerates Axonal Regeneration, Promotes Motor Reinnervation, and Reduces Muscle Atrophy following Peripheral Nerve Injury

Cited by 62 publications

References 58 publications

Neurotrophic and Neuroregenerative Effects of GH/IGF1

Neurotrophic and Neuroregenerative Effects of GH/IGF1

The course of recovery of locomotor function over a 10‐week observation period in a rat model of femoral nerve resection and autograft repair

Growth Hormone (GH) and Rehabilitation Promoted Distal Innervation in a Child Affected by Caudal Regression Syndrome

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