IGF-I and End-to-Side Nerve Repair: A Dose-Response Study

Tiangco, David A.; Papakonstantinou, Konstantinos C.; Mullinax, Kelly A.; Terzis, Julia K.

doi:10.1055/s-2001-14516

Cited by 47 publications

(51 citation statements)

References 34 publications

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“…IGF-1 plays an important role in the nervous system, stimulating postnatal brain growth (46), promoting neuron survival and growth (47,48), increasing the rate of axon regeneration in crush-injured sciatic nerve (49) and increasing the proliferation of oligodendrocytes (50). Lack of IGF-1 in knockout mice severely affects survival and maturation of neurons (51).…”

Section: Discussionmentioning

confidence: 99%

IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

Murdocca¹,

Malgieri²,

Luchetti³

et al. 2012

Mol Med

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Spinal muscular atrophy (SMA) is an inherited neurodegenerative disorder and the first genetic cause of death in childhood. SMA is caused by low levels of survival motor neuron (SMN) protein that induce selective loss of α-motor neurons (MNs) in the spinal cord, resulting in progressive muscle atrophy and consequent respiratory failure. To date, no effective treatment is available to counteract the course of the disease. Among the different therapeutic strategies with potential clinical applications, the evaluation of trophic and/or protective agents able to antagonize MNs degeneration represents an attractive opportunity to develop valid therapies. Here we investigated the effects of IPLEX (recombinant human insulinlike growth factor 1 [rhIGF-1] complexed with recombinant human IGF-1 binding protein 3 [rhIGFBP-3]) on a severe mouse model of SMA. Interestingly, molecular and biochemical analyses of IGF-1 carried out in SMA mice before drug administration revealed marked reductions of IGF-1 circulating levels and hepatic mRNA expression. In this study, we found that perinatal administration of IPLEX, even if does not influence survival and body weight of mice, results in reduced degeneration of MNs, increased muscle fiber size and in amelioration of motor functions in SMA mice. Additionally, we show that phenotypic changes observed are not SMN-dependent, since no significant SMN modification was addressed in treated mice. Collectively, our data indicate IPLEX as a good therapeutic candidate to hinder the progression of the neurodegenerative process in SMA.

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Section: Discussionmentioning

confidence: 99%

IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

Murdocca¹,

Malgieri²,

Luchetti³

et al. 2012

Mol Med

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“…The impact of the sensory nerve on the muscle trophism is under investigation 15,16 . The end-to-side neurorraphy can be applied in those selected cases in which no donor nerve is dispensable.…”

Section: Discussionmentioning

confidence: 99%

A gastrocnemius heterotopical transplant model with end-to-side neurorraphy

et al. 2014

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PURPOSE:To present an animal model to assess the effects of end-to-side innervation in the heterotopically transplanted model with reduced chances of neural contamination. METHODS:The medial portion of the gastrocnemius muscle in wistar male rats was isolated and its pedicle dissected and performed a flap in the abdominal portion. To prevent neural contamination in the abdominal region, the muscle was wrapped with a Goretex® sheet.The specimens were divided into 2 groups (G). In G1 was performed an end-to-end suture between tibial nerve of the gastrocnemius and femoral motor nerve and between the saphenous sensory nerve and the motor nerve. In G2 was performed a end-to-side suture between the tibial nerve and the motor femoral and between the tibial nerve and saphenous motor nerve. The specimens were evaluated 60 days later to check the structure of the neurorraphy. Sections were obtained proximal and distal to the coaptation site. RESULTS:The medial gastrocnemius muscle had the advantage of maintaining visible mass after 60 days. No disruption of the coaptation site was found. No major injury to the donor nerve was seen in group 2. CONCLUSION:The proposed model is simple, reproduciple and prevent the neural contamination in the flap in end-to-side suture.Key words: Animal model. Mycrosurgery. Rats. A gastrocnemius heterotopical transplant model with end-to-side neurorraphyActa

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“…241,242 In addition, it is closely correlated with neuronal responses to injury being up-regulated at the time of axonal sprouting and elongation. 21,[243][244][245][246] However, addition of exogenous IGF-1 fails to increase the accuracy of regeneration or functional outcomes such as muscle power, motor evoked potentials and conduction velocity. 247,248 Although IGF-1 mediates exercise-induced anabolic changes in muscle tissue, [249][250][251] it is not known whether this neurotrophic factor is involved in stimulation- After FFA and handling in IGF-1 +/-mice, the pattern was similar (whisking amplitude 57% lower than intact;…”

Section: Recovery Of Whisking Function Promoted By Manual Stimulationmentioning

confidence: 99%

Experimental studies on post-transectional facial nerve regrowth and functional recovery of paralyzed muscles of the face in rats and mice

Skouras¹,

Angelov²

2010

Anatomy

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The facial nerve is the most frequently damaged nerve in head and neck traumata. Apart from traffic-accident injuries (temporal bone fractures, or lacerations of the face), most facial nerve lesions are post-operative AbstractInsufficient recovery after peripheral nerve injury has been attributed to (i) lack of axonal navigation and poor pathfinding of regrowing axons to improper targets, (ii) excessive collateral axonal branching at the lesion site and (iii) polyneuronal reinnervation of the neuromuscular junctions (NMJ). The facial nerve transection model in rat and mice has been used to measure the restoration of function after varying therapies and to examine the mechanisms underlying their effects. Since it is still very difficult to combat the first reason and control/correct the navigation of several thousand axons, several groups of scientists concentrated our efforts on the postlesional branching (extremely strong in adult rats) and NMJ-polyinnervation. Since polyneuronal innervation of muscle fibers is activity-dependent attempts to reduce it were performed applying electrical stimulation. Unfortunately, the highly recommended intraoperative electrical stimulation of the proximal nerve fragment (square 0.1 ms pulses at 20 Hz using suprathreshold amplitudes) prior to suture and the postoperative electrical stimulation (square 0.1 ms pulses at 5 Hz) not only did not improve functional outcome, but reduced the number of innervated NMJ to approximately one fifth of normal values. Finally, recent experiments demonstrated that it was the mechanical (but not electrical) stimulation of denervated facial muscles (vibrissal and orbicularis oculi) which improved motor performance. This beneficial effect of mechanical stimulation was also detected after hypoglossal-facial anastomosis and inter-positional nerve grafting. The beneficial effect of manual stimulation on target muscle reinnervation was not present in mice deficient in the expression of insulin-like growth factor 1 and also eliminated or even reversed when trigeminal afferent inputs were abolished. All these findings raise hopes that clinically feasible and effective therapies could be soon designed and tested.

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IGF-I and End-to-Side Nerve Repair: A Dose-Response Study

Cited by 47 publications

References 34 publications

IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

IPLEX Administration Improves Motor Neuron Survival and Ameliorates Motor Functions in a Severe Mouse Model of Spinal Muscular Atrophy

A gastrocnemius heterotopical transplant model with end-to-side neurorraphy

Experimental studies on post-transectional facial nerve regrowth and functional recovery of paralyzed muscles of the face in rats and mice

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